Materiały źródłowe

• #1 Peripheral nerve injuries in children—prevalence, mechanisms and concomitant injuries: a major trauma center’s experience | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-01082-x

  Peripheral nerve injuries are severe conditions with potential lifelong impairment, which is especially meaningful for the pediatric population. Knowledge on prevalence, injury mechanisms and concomitant injuries is, therefore, of utmost importance to increase clinician awareness and enable early diagnosis and treatment. […] We observed that a large proportion of injures had complete transections, often accompanied by concomitant vessel injuries especially in distally located injuries, highlighting the importance of early surgical exploration. […] Knowledge on mechanisms and concomitant injuries facilitates timely diagnosis and treatment, thereby potentially preventing lifelong impairment. […] Peripheral nerve injuries are severe conditions often leading to lifetime impairment in case of incomplete recovery. This is especially relevant for children, who may potentially suffer for decades.

• #2 Biomedicines | Special Issue : The Pathophysiology of Peripheral Nerve Injuries

  https://www.mdpi.com/journal/biomedicines/special_issues/peripheral_nerve_patho

  The Pathophysiology of Peripheral Nerve Injuries […] Peripheral neuropathies comprise a group of disorders that severely damage peripheral nerve function and affect approximately 2.4 percent of the population. These disorders originate from a variety of factors including genetic, metabolic, systemic, and toxic causes, which drive the dysfunction of motor, sensory, and autonomic nerve fibers. Peripheral nerve dysfunction results mainly from axonal degeneration, demyelination, or a combination of both. Deciphering the cellular and molecular mechanisms underlying peripheral neuropathies is critical not only to increasing the knowledge of the pathogenesis of these diseases but also for the development of therapeutic interventions. […] This open-access Special Issue, consisting of original research and review articles, provides an opportunity for researchers in the field to share their research on the pathophysiology of peripheral neuropathies with broad coverage of aspects ranging from cell biology to a translational level.

• #3

  https://journals.lww.com/neur/fulltext/2019/67060/peripheral_nerve_injuries__electrophysiology_for.5.aspx

  Peripheral nerve injuries are often missed in patients with head injury or polytrauma leading to delay in recovery, morbidity, and poor functional outcome. An early diagnosis and management are important to improve the functional outcome in these patients, and hence, it is important to identify the associated nerve injury. Electrophysiological studies play a key role in peripheral nerve injuries and are useful in lesion localization, determining the type and severity of injury, and prognostication. […] The aim of this review is to describe concisely the classification, patterns of nerve regeneration, and the electrophysiological methods. […] The earliest classification of nerve injuries was given by Seddon and Sunderland. These classifications even hold true till date and are commonly used. In the Seddon classification, the peripheral nerve injuries are divided into three types: neuropraxia, axonotmesis, and neurotmesis.

• #4 Peripheral Nerve Entrapment and Injury in the Upper Extremity | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0301/p275.html

  Peripheral nerves in the upper extremities are at risk of injury and entrapment because of their superficial nature and length. Injury can result from trauma, anatomic abnormalities, systemic disease, and entrapment. The extent of the injury can range from mild neurapraxia, in which the nerve experiences mild ischemia caused by compression, to severe neurotmesis, in which the nerve has full-thickness damage and full recovery may not occur. […] Mechanisms of nerve injury can include direct pressure, stretch, overuse of a joint, or microtrauma. Prolongation of these injurious mechanisms causes fibrosis, resulting in a larger degree of injury. More specifically, nerve injury is divided into three grades of increasing severity: neurapraxia, axonotmesis, and neurotmesis. Neurapraxia is injury that damages the myelin sheath but not the axon. Complete recovery is possible in days to weeks. Axonotmesis extends damage to the axon but preserves the connective tissue framework. This can lead to subsequent degeneration distal to the lesion. Because of the slow rate of axonal regeneration, recovery can take years, with complete recovery often unachievable. Neurotmesis is the total or partial disruption of the entire nerve fiber, including the connective tissue framework. Full clinical recovery is usually not achieved. […] How long compression must be present to cause permanent loss of conduction or fibrosis is not well defined in the literature.

• #5 Peripheral Nerve Entrapment and Injury in the Upper Extremity | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0301/p275.html

  Peripheral nerves in the upper extremities are at risk of injury and entrapment because of their superficial nature and length. Injury can result from trauma, anatomic abnormalities, systemic disease, and entrapment. The extent of the injury can range from mild neurapraxia, in which the nerve experiences mild ischemia caused by compression, to severe neurotmesis, in which the nerve has full-thickness damage and full recovery may not occur. […] Mechanisms of nerve injury can include direct pressure, stretch, overuse of a joint, or microtrauma. Prolongation of these injurious mechanisms causes fibrosis, resulting in a larger degree of injury. More specifically, nerve injury is divided into three grades of increasing severity: neurapraxia, axonotmesis, and neurotmesis. Neurapraxia is injury that damages the myelin sheath but not the axon. Complete recovery is possible in days to weeks. Axonotmesis extends damage to the axon but preserves the connective tissue framework. This can lead to subsequent degeneration distal to the lesion. Because of the slow rate of axonal regeneration, recovery can take years, with complete recovery often unachievable. Neurotmesis is the total or partial disruption of the entire nerve fiber, including the connective tissue framework. Full clinical recovery is usually not achieved. […] How long compression must be present to cause permanent loss of conduction or fibrosis is not well defined in the literature.

• #6 Neuropraxia: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22608-neuropraxia

  Neuropraxia is an injury to your peripheral nerves. These nerves carry electrical signals (impulses) from your brain and spinal cord to the rest of your body. […] Neuropraxia can happen for many reasons. Nerves may become crushed or compressed. When this happens, they cant send electrical impulses. Traumatic neuropraxia can result from: Bone fractures. Dislocation. Tears and injuries to ligaments and tendons. […] Most people with neuropraxia recover fully. But some people develop complications such as: Inflammation. Long-term nerve pain, numbness or weakness. Scars in the tissue near the injury site. […] Neuropraxia is a mild peripheral nerve injury that usually heals on its own with time and rest.

• #7

  https://journals.lww.com/neur/fulltext/2019/67060/peripheral_nerve_injuries__electrophysiology_for.5.aspx

  In axonotmesis, the axons are damaged; however, most of the covering connective tissues that form the endoneurium, perineurium, and epineurium are still partially or fully intact. There are endoneurial tubes on which the nerve regeneration can take place. This type of nerve injury is seen in crush and stretch injuries. […] Neurotmesis is the most severe form of nerve injuries with severe damage to the axons, myelin sheath, and the connective tissue elements. The axonal growth is nearly inadequate. This type of nerve injury is seen after massive trauma, sharp injuries, traction or avulsion injuries, and injection of noxious drugs. Surgical repair is essential to enhance the reinnervation and recovery. […] The process of Wallerian degeneration is observed in axonotmesis. The cell body is separated from the axon segment distal to the injury. The transport of essential molecules and the electrical signal from the cell body to the axon fragment is disrupted.

• #8 Peripheral nerve injuries – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/peripheral-nerve-injuries/

  Results in Wallerian degeneration: an active neuronal degeneration process in response to axonal injury. […] Regeneration is significantly more efficient in the peripheral nervous system than in the central nervous system. […] Neurotmesis: Complete nerve transection. […] The chances of recovery are very poor without surgical repair.

• #9 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Peripheral nerve injuries are common conditions with broad ranging groups of symptoms depending on the severity and nerves involved. […] Although much knowledge exists on the mechanisms of injury and regeneration, reliable treatments that ensure full functional recovery are scarce. […] The most severe form of injury is called neurotmesis, which is a full transection of the axons and connective tissue layers wherein complete discontinuity of the nerve is observed. […] Compression injuries are not always captured by the commonly used classification schemes. […] Nonetheless, there is little doubt that the majority of peripheral nerve compressions fall under the general class of neurapraxia, or Grade I nerve injuries, and commonly occur in locations where nerves pass through narrow anatomical openings.

• #10 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  Nerve injury produces a long-lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperplasia, and an increase in response to noxious stimuli. […] The mechanism underlying the lasting abnormal pain is not well understood. […] Neurotmesis is the most severe grade of peripheral nerve injury. It occurs when the axon, myelin, and connective tissue components are damaged and disrupted or transected. […] Recovery through axonal regeneration cannot occur. […] Each mechanism of injury can cause specific nerve damage. […] The first mechanism of injury is mechanical injury. […] The second mechanism of injury is crush and percussion injury. […] Compartment syndrome injuries cause high pressure in the surrounding tissue. […] The third mechanism of injury is laceration injury caused by blunt or penetrating trauma.

• #11 Peripheral nerve injuries – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/peripheral-nerve-injuries/symptoms-causes/syc-20355631

  Peripheral nerves are fragile and easily damaged. A nerve injury can affect the brain’s ability to communicate with muscles and organs. Damage to the peripheral nerves is called peripheral neuropathy. […] Peripheral nerves can be damaged in several ways: Injury from an accident, a fall or sports can stretch, compress, crush or cut nerves. Medical conditions, such as diabetes, Guillain-Barre syndrome and carpal tunnel syndrome, can damage nerves. Autoimmune diseases including lupus, rheumatoid arthritis and Sjogren syndrome also can damage nerves. […] People who experience physical trauma or play sports may be at higher risk of an injury that can stretch or crush peripheral nerves. People with certain medical conditions also may be at higher risk of peripheral nerve injuries. These conditions, especially diabetes, may put nerves at greater risk of compression.

• #12

  https://www.orthobullets.com/hand/6066/peripheral-nerve-injury-and-repair

  Peripheral nerve injury is a relatively common condition that encompasses a range of reversible and irreversible impairments determined by injury level, axonal disruption, and time to treatment. […] Diagnosis is typically clinical with a combination of known injury with a nerve deficit. Advanced imaging such as ultrasound or MRI may be used to characterize nerve morphology after injury; however, EMG/NCS is a mainstay of evaluating both nerve injury and nerve recovery. Surgical exploration is confirmatory for traumatic nerve injuries. […] Treatment may involve observation, primary repair, nerve reconstruction with grafting, tendon transfers, nerve transfers, or a combination thereof depending on acuity, degree of injury, nerve quality, and mechanism of injury. […] Mechanism of injury includes stretching injury, where 8% elongation will diminish nerve’s microcirculation by 50% in rat sciatic nerve model; 15% elongation will disrupt bloodflow by 80% in the same model.

• #13 Mechanisms of Peripheral Nerve Injury – What to Treat, When to Treat | IntechOpen

  https://www.intechopen.com/chapters/46781

  Trauma to a peripheral nerve has effects on sensory neurons, on motor neurons controlling skeletal muscle and on autonomic efferent neurons controlling the cardiovascular system and organs. […] Multiple pathophysiological, neurochemical, and anatomical changes are triggered by peripheral nerve injury, whereby a simple focal peripheral nerve injury unleashes a range of peripheral as well as central nervous system processes that contribute to persistent pain and abnormal sensation. […] Understanding pathophysiology arising from peripheral nerve trauma is further complicated by the various types of trauma, which consist largely of a total cut of a peripheral nerve, a partial cut, an event-triggered compression, a slowly-developing compression (such as from a tumour), and a degeneration of nerve cells or of neural support cells and neural support tissues.

• #14

  https://www.orthobullets.com/hand/6066/peripheral-nerve-injury-and-repair

  Peripheral nerve injury is a relatively common condition that encompasses a range of reversible and irreversible impairments determined by injury level, axonal disruption, and time to treatment. […] Diagnosis is typically clinical with a combination of known injury with a nerve deficit. Advanced imaging such as ultrasound or MRI may be used to characterize nerve morphology after injury; however, EMG/NCS is a mainstay of evaluating both nerve injury and nerve recovery. Surgical exploration is confirmatory for traumatic nerve injuries. […] Treatment may involve observation, primary repair, nerve reconstruction with grafting, tendon transfers, nerve transfers, or a combination thereof depending on acuity, degree of injury, nerve quality, and mechanism of injury. […] Mechanism of injury includes stretching injury, where 8% elongation will diminish nerve’s microcirculation by 50% in rat sciatic nerve model; 15% elongation will disrupt bloodflow by 80% in the same model.

• #15

  https://www.orthobullets.com/hand/6066/peripheral-nerve-injury-and-repair

  Compression/crush injuries lead to local ischemia and increased vascular permeability, with endoneurial edema resulting in poor axonal transport and nerve dysfunction. […] Chronic compression leads to Schwann cell proliferation and apoptosis. […] Laceration injuries result in sharp transections, which have a better prognosis than crush injuries, as continuity of the nerve is disrupted and the nerve stops producing neurotransmitters. […] The regeneration process after transection involves Wallerian degeneration, where the distal segment undergoes degradation, and existing Schwann cells proliferate to line the endoneurial basement membrane. […] Variables affecting regeneration include contact guidance with attraction to the basal lamina of the Schwann cell, neurotropism, and neurotrophic factors.

• #16

  https://www.orthobullets.com/hand/6066/peripheral-nerve-injury-and-repair

  Compression/crush injuries lead to local ischemia and increased vascular permeability, with endoneurial edema resulting in poor axonal transport and nerve dysfunction. […] Chronic compression leads to Schwann cell proliferation and apoptosis. […] Laceration injuries result in sharp transections, which have a better prognosis than crush injuries, as continuity of the nerve is disrupted and the nerve stops producing neurotransmitters. […] The regeneration process after transection involves Wallerian degeneration, where the distal segment undergoes degradation, and existing Schwann cells proliferate to line the endoneurial basement membrane. […] Variables affecting regeneration include contact guidance with attraction to the basal lamina of the Schwann cell, neurotropism, and neurotrophic factors.

• #17 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. […] The fifth mechanism of injury is stretch injury. […] A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. […] A seventh mechanism of injury is cold injury. […] Each of the mechanisms of injury causes specific damage to a nerve. […] Wallerian degeneration occurs in peripheral nerves. […] Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/day. […] Axonal regeneration is guided toward the distal end of the nerve by a gradient of diffusible substances. […] Misdirected axonal buds can result in abnormal nerve connections. […] Motor endplates must be reinnervated within 18 months of trauma for function to be resumed. […] In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium.

• #18 Peripheral nerve injuries in children—prevalence, mechanisms and concomitant injuries: a major trauma center’s experience | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-01082-x

  Without early surgical treatment this may lead to lifelong impairment. […] We could demonstrate high costs for injuries and compensation for adult patients suffering from peripheral nerve injuries of more than 16 000 euros per year in a previous work. […] An interesting finding was the high prevalence of lesions due to burns and electricity injuries in the peroneal and tibial nerve. This has been previously described by Marquez et al.

• #19 Peripheral nerve injuries – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/peripheral-nerve-injuries/symptoms-causes/syc-20355631

  Peripheral nerves are fragile and easily damaged. A nerve injury can affect the brain’s ability to communicate with muscles and organs. Damage to the peripheral nerves is called peripheral neuropathy. […] Peripheral nerves can be damaged in several ways: Injury from an accident, a fall or sports can stretch, compress, crush or cut nerves. Medical conditions, such as diabetes, Guillain-Barre syndrome and carpal tunnel syndrome, can damage nerves. Autoimmune diseases including lupus, rheumatoid arthritis and Sjogren syndrome also can damage nerves. […] People who experience physical trauma or play sports may be at higher risk of an injury that can stretch or crush peripheral nerves. People with certain medical conditions also may be at higher risk of peripheral nerve injuries. These conditions, especially diabetes, may put nerves at greater risk of compression.

• #20 Traumatic peripheral nerve injuries in young Korean soldiers: a recent 10-year retrospective study

  https://jtraumainj.org/journal/view.php?number=1315

  Traumatic peripheral nerve injury (PNI), which occurs in up to 3% of trauma patients, is a devastating condition that often leads to permanent disability. […] Knowledge of traumatic PNI is limited. […] The most common PNI mechanism (n=49, 57.6%), was adjacent fractures or dislocations. […] Several injury-related characteristics were significantly associated with complete PNI: laceration or gunshot wound, PNI involving the median nerve, PNI involving multiple individual nerves (multiple PNI), and concomitant muscular or vascular injuries. […] After adjusting for other possible predictors, multiple PNI was identified as a significant predictor of a complete PNI (odds ratio, 3.583; P=0.017). […] The most common mechanism of PNI was adjacent fracture/dislocation (57.6%), followed by blunt trauma, lacerations, and gunshot wounds.

• #21 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways.

• #22 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Axons that incur traumatic damage will undergo Wallerian degeneration to create a microenvironment conducive for axonal regrowth and reinnervation. […] The hallmark of this phase is the granular disintegration of the cytoskeleton. […] Schwann cells are primary mediators in triggering many of the events in Wallerian degeneration and changes in their protein expression at the site of injury are key to axon regeneration. […] After the clearance of myelin debris, the dedifferentiated Schwann cells proliferate on the remaining endoneurial tubes of the extracellular matrix. […] Greater success in reinnervation from a regenerative axon is observed when the endoneurial tube is intact and neuroma formation is favored without the tube. […] Although the alteration in the genetic expression of the neuron from a quiescent state to a regenerative state occurs concurrently with the events of Wallerian degeneration, axonal regeneration itself begins after Wallerian degeneration is completed.

• #23 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  During Wallerian degeneration, axoplasm undergoes disintegration and degeneration within 24 h in small nerve fibers and 48 h in larger nerve fibers. […] The axonal breakdown is mediated by calcium (Ca2+) influx and further processed by activation of multiple axonal proteases, such as calpain, leading to the degradation of neurofilaments, mitochondria, endoplasmic reticulum, and cytoskeleton of the axon. […] Simultaneously occurring with axonal degeneration, SCs allow Ca2+ to flow inward to activate the release of proteases. […] In response to injury, SCs undergo dynamic cell reprogramming and morphological changes to promote nerve regeneration and functional recovery. […] The phenotype of SCs includes myelinated SCs and non-myelinated SCs. […] After injury, activated SCs upregulate the cascade reaction of cytokines and chemokines that recruit macrophages.

• #24 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  During Wallerian degeneration, axoplasm undergoes disintegration and degeneration within 24 h in small nerve fibers and 48 h in larger nerve fibers. […] The axonal breakdown is mediated by calcium (Ca2+) influx and further processed by activation of multiple axonal proteases, such as calpain, leading to the degradation of neurofilaments, mitochondria, endoplasmic reticulum, and cytoskeleton of the axon. […] Simultaneously occurring with axonal degeneration, SCs allow Ca2+ to flow inward to activate the release of proteases. […] In response to injury, SCs undergo dynamic cell reprogramming and morphological changes to promote nerve regeneration and functional recovery. […] The phenotype of SCs includes myelinated SCs and non-myelinated SCs. […] After injury, activated SCs upregulate the cascade reaction of cytokines and chemokines that recruit macrophages.

• #25 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  During Wallerian degeneration, axoplasm undergoes disintegration and degeneration within 24 h in small nerve fibers and 48 h in larger nerve fibers. […] The axonal breakdown is mediated by calcium (Ca2+) influx and further processed by activation of multiple axonal proteases, such as calpain, leading to the degradation of neurofilaments, mitochondria, endoplasmic reticulum, and cytoskeleton of the axon. […] Simultaneously occurring with axonal degeneration, SCs allow Ca2+ to flow inward to activate the release of proteases. […] In response to injury, SCs undergo dynamic cell reprogramming and morphological changes to promote nerve regeneration and functional recovery. […] The phenotype of SCs includes myelinated SCs and non-myelinated SCs. […] After injury, activated SCs upregulate the cascade reaction of cytokines and chemokines that recruit macrophages.

• #26 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways.

• #27

  https://link.springer.com/10.1007/s00441-025-03957-3

  Limb injuries such as severe strains, deep cuts, gunshot wounds, and ischemia can cause peripheral nerve damage. […] Schwann cells are responsible for repairing and regenerating damaged nerves in the peripheral nervous system. They play a crucial role in the healing of nerve injuries and are essential for the restoration of proper nerve function. […] An increasing number of studies have focused on the various regulatory mechanisms that specifically affect the repair of damage by Schwann cells. […] We also discuss the various molecular mechanisms that regulate Schwann cell function during peripheral nerve repair and how they can be used to promote nerve repair and regeneration. […] Furthermore, we explore the potential therapeutic applications of precision regulation of Schwann cells for the treatment of peripheral nerve injuries.

• #28 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  During Wallerian degeneration, axoplasm undergoes disintegration and degeneration within 24 h in small nerve fibers and 48 h in larger nerve fibers. […] The axonal breakdown is mediated by calcium (Ca2+) influx and further processed by activation of multiple axonal proteases, such as calpain, leading to the degradation of neurofilaments, mitochondria, endoplasmic reticulum, and cytoskeleton of the axon. […] Simultaneously occurring with axonal degeneration, SCs allow Ca2+ to flow inward to activate the release of proteases. […] In response to injury, SCs undergo dynamic cell reprogramming and morphological changes to promote nerve regeneration and functional recovery. […] The phenotype of SCs includes myelinated SCs and non-myelinated SCs. […] After injury, activated SCs upregulate the cascade reaction of cytokines and chemokines that recruit macrophages.

• #29 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Axons that incur traumatic damage will undergo Wallerian degeneration to create a microenvironment conducive for axonal regrowth and reinnervation. […] The hallmark of this phase is the granular disintegration of the cytoskeleton. […] Schwann cells are primary mediators in triggering many of the events in Wallerian degeneration and changes in their protein expression at the site of injury are key to axon regeneration. […] After the clearance of myelin debris, the dedifferentiated Schwann cells proliferate on the remaining endoneurial tubes of the extracellular matrix. […] Greater success in reinnervation from a regenerative axon is observed when the endoneurial tube is intact and neuroma formation is favored without the tube. […] Although the alteration in the genetic expression of the neuron from a quiescent state to a regenerative state occurs concurrently with the events of Wallerian degeneration, axonal regeneration itself begins after Wallerian degeneration is completed.

• #30 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In addition to clearing myelin debris, macrophages and SCs also produce cytokines that promote axonal growth. […] In the early stages of Wallerian degeneration, SCs mainly produce monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and neurogenic cytokines such as interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), which contribute to the selective accumulation of macrophages at the distal stump of damaged peripheral nerves. […] Furthermore, the interaction between macrophages and SCs can control the inflammatory response and phagocytosis of myelin debris at the lesion site, thereby promoting axonal branching. […] During peripheral nerve regeneration, the growth of SCs depends on a well-developed extracellular matrix (ECM) environment, which is a physiologically integrated matrix with complex molecular properties, allowing the basal lamina tubes to serve as scaffolds in which SCs arrange to form Bngner bands.

• #31 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways.

• #32 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  During Wallerian degeneration, axoplasm undergoes disintegration and degeneration within 24 h in small nerve fibers and 48 h in larger nerve fibers. […] The axonal breakdown is mediated by calcium (Ca2+) influx and further processed by activation of multiple axonal proteases, such as calpain, leading to the degradation of neurofilaments, mitochondria, endoplasmic reticulum, and cytoskeleton of the axon. […] Simultaneously occurring with axonal degeneration, SCs allow Ca2+ to flow inward to activate the release of proteases. […] In response to injury, SCs undergo dynamic cell reprogramming and morphological changes to promote nerve regeneration and functional recovery. […] The phenotype of SCs includes myelinated SCs and non-myelinated SCs. […] After injury, activated SCs upregulate the cascade reaction of cytokines and chemokines that recruit macrophages.

• #33 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In the process of peripheral nerve regeneration, there are many signaling pathways participating in the mechanism of peripheral nerve repair. […] Research on the axonal transection response of cultured sea rabbit neurons indicated that axonal damage leads to a rapid increase of axonal Ca2+ levels, while Ca2+ increases the activity of adenylate cyclase, triggering the production of cAMP. […] Neurotrophic factors, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), play critical roles in modulating neural plasticity and promoting neural repair and functional recovery via binding to tyrosine kinase receptors. […] The high affinity receptor of NGF is tropomyosin receptor kinase A (TrkA), the binding of NGF activates the ERK1/2-CREB-Trx-1 pathway to promote neurite growth.

• #34 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  The inflammatory response is a predominantly defense-based physiological response of the body to harmful stimuli, a protective behavior in which multiple cells are involved. […] Neuroinflammation is a condition in which the levels of pro-inflammatory and anti-inflammatory factors in the body increase dramatically after an injury, while activating neuroglial cells such as microglia and astrocytes to cause an immune response, thereby resulting in symptoms such as inflammation and pain. […] It has been shown that the mechanisms of neuroinflammation contribute to nerve repair, the most prominent of which is the phagocytosis of tissue debris by immune-associated cells and the massive secretion of nerve growth factor to create a favorable microenvironment for neuronal axon regeneration after nerve injury.

• #35 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways.

• #36 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In addition to clearing myelin debris, macrophages and SCs also produce cytokines that promote axonal growth. […] In the early stages of Wallerian degeneration, SCs mainly produce monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and neurogenic cytokines such as interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), which contribute to the selective accumulation of macrophages at the distal stump of damaged peripheral nerves. […] Furthermore, the interaction between macrophages and SCs can control the inflammatory response and phagocytosis of myelin debris at the lesion site, thereby promoting axonal branching. […] During peripheral nerve regeneration, the growth of SCs depends on a well-developed extracellular matrix (ECM) environment, which is a physiologically integrated matrix with complex molecular properties, allowing the basal lamina tubes to serve as scaffolds in which SCs arrange to form Bngner bands.

• #37 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Macrophage polarization plays an important role in the repair of peripheral nerve injuries. M1 macrophages are involved in the development of neuroinflammation and pain after PNI through the high expression of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. M2 macrophages are usually considered to be beneficial to nerve repair after PNI. […] After PNI, the local hypoxia and tissue necrosis secondary to inflammation impede nerve repair and regeneration. […] The activation of NLRP3 inflammasomes promotes the recruitment of macrophages and neutrophils by regulating the release of IL-33. […] The complement system, which consists of more than 40 soluble and membrane-associated components, modulators, and receptors, also contributes to recovery from infection or injury, regulates adaptive immune responses, and limits microbial infections.

• #38 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In addition to clearing myelin debris, macrophages and SCs also produce cytokines that promote axonal growth. […] In the early stages of Wallerian degeneration, SCs mainly produce monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and neurogenic cytokines such as interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), which contribute to the selective accumulation of macrophages at the distal stump of damaged peripheral nerves. […] Furthermore, the interaction between macrophages and SCs can control the inflammatory response and phagocytosis of myelin debris at the lesion site, thereby promoting axonal branching. […] During peripheral nerve regeneration, the growth of SCs depends on a well-developed extracellular matrix (ECM) environment, which is a physiologically integrated matrix with complex molecular properties, allowing the basal lamina tubes to serve as scaffolds in which SCs arrange to form Bngner bands.

• #39 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  Macrophage polarization plays an important role in the repair of peripheral nerve injuries. M1 macrophages are involved in the development of neuroinflammation and pain after PNI through the high expression of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. M2 macrophages are usually considered to be beneficial to nerve repair after PNI. […] After PNI, the local hypoxia and tissue necrosis secondary to inflammation impede nerve repair and regeneration. […] The activation of NLRP3 inflammasomes promotes the recruitment of macrophages and neutrophils by regulating the release of IL-33. […] The complement system, which consists of more than 40 soluble and membrane-associated components, modulators, and receptors, also contributes to recovery from infection or injury, regulates adaptive immune responses, and limits microbial infections.

• #40 Inflammation in the Peripheral Nervous System after Injury

  https://www.mdpi.com/2227-9059/12/6/1256

  After injury in the PNS, the complement cascade is quickly (within 1 h) activated locally at the site of damage. Myelin proteins can activate the complement system through the classical and the alternative pathway in an antibody-independent manner, and the myelin phagocytosis by macrophages is mediated by the complement via complement type 3 receptor (CR3). […] In the early stages after nerve injury, inflammation is beneficial because it removes tissue debris and increases levels of neurotrophic factors. However, when the inflammatory response persists, the inflammatory cells release large amounts of inflammatory cytokines, causing further damage to the microenvironment, which is not conductive to nerve recovery and even damaging to healthy nerves. Therefore, excessive inflammation is detrimental to the recovery of body functions after nerve injury.

• #41 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  Peripheral nerve injury (PNI) usually causes severe motor, sensory and autonomic dysfunction. […] Recently, significant progress has been made in new physical modulation to promote peripheral nerve regeneration. […] We hereby review current progress on the mechanism of peripheral nerve regeneration after injury and summarize the new findings and evidence for the application of physical modulation, including electrical stimulation, light, ultrasound, magnetic stimulation, and mechanical stretching in experimental studies and the clinical treatment of patients with PNI. […] Although the peripheral nervous system (PNS) exhibits greater regenerative ability than the central nervous system (CNS) after injury, the regenerative ability of PNS is still limited, due to the slow speed of axonal regeneration, and the limited regenerative ability of neurons over time.

• #42 Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery

  https://www.ijbs.com/v16p0116.htm

  The process of chemotactic and communication repulsion and attraction regulates the fortune of an axon that needs to be regenerated. The frequency of regeneration of axon is estimated by alterations within the soma, growth cone stability at the axonal sprout tip, and the hindrance of damaged tissue between end organ and soma. In humans, axonal regeneration occurs at a rate of almost 1 mm/day. Thus moderate to severe type of injuries take months or even years to heal. The PNI lead to the extensive changes in the neuronal expression of thousands of the genes which includes numerous transcription factors. […] Even after a long healing period full functional re-innervation without any complication is not possible. In the case of grade III injury, retraction of the severed nerve fiber ends happens due to elastic endoneurium which causes local trauma. It leads to a significant inflammatory response. Fibroblast proliferation aggravates the process and a dense inter-fascicular scar is formed. This kind of injury distracts the axonal regeneration and endoneurial tubes remain denervated. If the endoneurial tube does not receive a regenerating axon, the progressive fibrosis ultimately demolishes it. In the IV and V grade injuries, activated Schwann cells and fibroblasts cause vigorous cellular proliferation.

• #43 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. […] The fifth mechanism of injury is stretch injury. […] A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. […] A seventh mechanism of injury is cold injury. […] Each of the mechanisms of injury causes specific damage to a nerve. […] Wallerian degeneration occurs in peripheral nerves. […] Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/day. […] Axonal regeneration is guided toward the distal end of the nerve by a gradient of diffusible substances. […] Misdirected axonal buds can result in abnormal nerve connections. […] Motor endplates must be reinnervated within 18 months of trauma for function to be resumed. […] In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium.

• #44 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  More recent studies have shown that shear stress alone can induce Schwann cell demyelination, proliferation and re-myelination. […] The examination of these two mechanisms begets the question of why the Schwann cells are chiefly affected and not the neurons themselves. […] When an end-organ becomes denervated, reinnervation can occur in two ways: through collateral branching of intact axons or by regeneration of the injured axon. […] In injuries where 20-30% of the axons are damaged, collateral branching is the primary mechanism of recovery. […] In injuries affecting greater than 90% of the axon population within a nerve, axonal regeneration is the primary means for recovery. […] Failure of any of these processes can contribute to the poor functional outcome commonly observed in patients with peripheral nerve injuries.

• #45 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  More recent studies have shown that shear stress alone can induce Schwann cell demyelination, proliferation and re-myelination. […] The examination of these two mechanisms begets the question of why the Schwann cells are chiefly affected and not the neurons themselves. […] When an end-organ becomes denervated, reinnervation can occur in two ways: through collateral branching of intact axons or by regeneration of the injured axon. […] In injuries where 20-30% of the axons are damaged, collateral branching is the primary mechanism of recovery. […] In injuries affecting greater than 90% of the axon population within a nerve, axonal regeneration is the primary means for recovery. […] Failure of any of these processes can contribute to the poor functional outcome commonly observed in patients with peripheral nerve injuries.

• #46 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. […] The fifth mechanism of injury is stretch injury. […] A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. […] A seventh mechanism of injury is cold injury. […] Each of the mechanisms of injury causes specific damage to a nerve. […] Wallerian degeneration occurs in peripheral nerves. […] Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/day. […] Axonal regeneration is guided toward the distal end of the nerve by a gradient of diffusible substances. […] Misdirected axonal buds can result in abnormal nerve connections. […] Motor endplates must be reinnervated within 18 months of trauma for function to be resumed. […] In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium.

• #47 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. […] The fifth mechanism of injury is stretch injury. […] A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. […] A seventh mechanism of injury is cold injury. […] Each of the mechanisms of injury causes specific damage to a nerve. […] Wallerian degeneration occurs in peripheral nerves. […] Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/day. […] Axonal regeneration is guided toward the distal end of the nerve by a gradient of diffusible substances. […] Misdirected axonal buds can result in abnormal nerve connections. […] Motor endplates must be reinnervated within 18 months of trauma for function to be resumed. […] In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium.

• #48

  https://www.orthobullets.com/hand/6066/peripheral-nerve-injury-and-repair

  Compression/crush injuries lead to local ischemia and increased vascular permeability, with endoneurial edema resulting in poor axonal transport and nerve dysfunction. […] Chronic compression leads to Schwann cell proliferation and apoptosis. […] Laceration injuries result in sharp transections, which have a better prognosis than crush injuries, as continuity of the nerve is disrupted and the nerve stops producing neurotransmitters. […] The regeneration process after transection involves Wallerian degeneration, where the distal segment undergoes degradation, and existing Schwann cells proliferate to line the endoneurial basement membrane. […] Variables affecting regeneration include contact guidance with attraction to the basal lamina of the Schwann cell, neurotropism, and neurotrophic factors.

• #49 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Axons that incur traumatic damage will undergo Wallerian degeneration to create a microenvironment conducive for axonal regrowth and reinnervation. […] The hallmark of this phase is the granular disintegration of the cytoskeleton. […] Schwann cells are primary mediators in triggering many of the events in Wallerian degeneration and changes in their protein expression at the site of injury are key to axon regeneration. […] After the clearance of myelin debris, the dedifferentiated Schwann cells proliferate on the remaining endoneurial tubes of the extracellular matrix. […] Greater success in reinnervation from a regenerative axon is observed when the endoneurial tube is intact and neuroma formation is favored without the tube. […] Although the alteration in the genetic expression of the neuron from a quiescent state to a regenerative state occurs concurrently with the events of Wallerian degeneration, axonal regeneration itself begins after Wallerian degeneration is completed.

• #50 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  The presence of an intact endoneurial tube more often leads to a better outcome in nerve regeneration. […] The more distal the injury to the neuron, the more likely it is to recover with the very proximal lesions, close to the neuronal cell bodies, often triggering programmed neuronal cell death. […] Even if the regenerated axon is able to reach the target, maturation is only possible if the end-organ is maintained. […] Muscle fibers undergo atrophy as early as 3 weeks after denervation, with collagen deposits forming in the endomysium and the perimysium. […] Taken together, advancements in the understanding of nerve injury and recovery continue to provide new avenues for surgeons to explore future prospective therapies.

• #51 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  The presence of an intact endoneurial tube more often leads to a better outcome in nerve regeneration. […] The more distal the injury to the neuron, the more likely it is to recover with the very proximal lesions, close to the neuronal cell bodies, often triggering programmed neuronal cell death. […] Even if the regenerated axon is able to reach the target, maturation is only possible if the end-organ is maintained. […] Muscle fibers undergo atrophy as early as 3 weeks after denervation, with collagen deposits forming in the endomysium and the perimysium. […] Taken together, advancements in the understanding of nerve injury and recovery continue to provide new avenues for surgeons to explore future prospective therapies.

• #52 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  The presence of an intact endoneurial tube more often leads to a better outcome in nerve regeneration. […] The more distal the injury to the neuron, the more likely it is to recover with the very proximal lesions, close to the neuronal cell bodies, often triggering programmed neuronal cell death. […] Even if the regenerated axon is able to reach the target, maturation is only possible if the end-organ is maintained. […] Muscle fibers undergo atrophy as early as 3 weeks after denervation, with collagen deposits forming in the endomysium and the perimysium. […] Taken together, advancements in the understanding of nerve injury and recovery continue to provide new avenues for surgeons to explore future prospective therapies.

• #53 Peripheral Nerve Injury | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/peripheral-nerve-injury

  Nerve injuries interfere with these signals and can lead to a loss of movement or feeling in the affected area. […] When an injury interferes with communication between a nerve and a muscle in the arm or leg, it’s called a peripheral nerve injury. […] Some nerve injuries are temporary — if the injury is mild to moderate, a nerve may repair itself. But if the nerve damage is severe, and nerve signals aren’t restored in 12 to 18 months, the muscle will never regain function. […] Nerve injuries can happen in a number of ways: Many nerve injuries happen at the same time as bone or muscle injuries. […] During a difficult birth, the network of nerves located between the neck and shoulder can get damaged, a condition called brachial plexus birth injury. […] Severely damaged nerves and nerves that have been ruptured or cut can sometimes be repaired with surgery. Nerve repair surgery creates a new pathway for signals to travel to and from the brain and the muscle. […] Nerves grow much more slowly than bones and muscles, therefore, recovery from nerve repair surgery can take up to two years.

• #54 The Treatment of Peripheral Nerve Injuries (09.08.2024)

  https://di.aerzteblatt.de/int/archive/article/240616/The-treatment-of-peripheral-nerve-injuries

  Nerve lesions often heal incompletely, leading to lifelong functional impairment, chronic pain, and high costs for the health care system. […] This is due to the pathophysiology of nerve regeneration. After a nerve is transected, the distal nerve end is subject to Wallerian degeneration with loss of axonal structures and the myelin sheath. The axons sprout from the proximal nerve end and grow distally through the remaining basal lamina tubes at a regeneration rate of approximately 13 mm/day. If motor axons reach their muscle end organ within 12-18 months, good function can return. Thereafter, the motor end plate degenerates completely, meaning that the possibility of reinnervation is lost. Therefore, the right timing for nerve reconstruction plays a particularly important role in motor nerve damage.

• #55 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In the process of peripheral nerve regeneration, there are many signaling pathways participating in the mechanism of peripheral nerve repair. […] Research on the axonal transection response of cultured sea rabbit neurons indicated that axonal damage leads to a rapid increase of axonal Ca2+ levels, while Ca2+ increases the activity of adenylate cyclase, triggering the production of cAMP. […] Neurotrophic factors, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), play critical roles in modulating neural plasticity and promoting neural repair and functional recovery via binding to tyrosine kinase receptors. […] The high affinity receptor of NGF is tropomyosin receptor kinase A (TrkA), the binding of NGF activates the ERK1/2-CREB-Trx-1 pathway to promote neurite growth.

• #56 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In the process of peripheral nerve regeneration, there are many signaling pathways participating in the mechanism of peripheral nerve repair. […] Research on the axonal transection response of cultured sea rabbit neurons indicated that axonal damage leads to a rapid increase of axonal Ca2+ levels, while Ca2+ increases the activity of adenylate cyclase, triggering the production of cAMP. […] Neurotrophic factors, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), play critical roles in modulating neural plasticity and promoting neural repair and functional recovery via binding to tyrosine kinase receptors. […] The high affinity receptor of NGF is tropomyosin receptor kinase A (TrkA), the binding of NGF activates the ERK1/2-CREB-Trx-1 pathway to promote neurite growth.

• #57 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In the process of peripheral nerve regeneration, there are many signaling pathways participating in the mechanism of peripheral nerve repair. […] Research on the axonal transection response of cultured sea rabbit neurons indicated that axonal damage leads to a rapid increase of axonal Ca2+ levels, while Ca2+ increases the activity of adenylate cyclase, triggering the production of cAMP. […] Neurotrophic factors, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), play critical roles in modulating neural plasticity and promoting neural repair and functional recovery via binding to tyrosine kinase receptors. […] The high affinity receptor of NGF is tropomyosin receptor kinase A (TrkA), the binding of NGF activates the ERK1/2-CREB-Trx-1 pathway to promote neurite growth.

• #58 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  In the process of peripheral nerve regeneration, there are many signaling pathways participating in the mechanism of peripheral nerve repair. […] Research on the axonal transection response of cultured sea rabbit neurons indicated that axonal damage leads to a rapid increase of axonal Ca2+ levels, while Ca2+ increases the activity of adenylate cyclase, triggering the production of cAMP. […] Neurotrophic factors, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), play critical roles in modulating neural plasticity and promoting neural repair and functional recovery via binding to tyrosine kinase receptors. […] The high affinity receptor of NGF is tropomyosin receptor kinase A (TrkA), the binding of NGF activates the ERK1/2-CREB-Trx-1 pathway to promote neurite growth.

• #59 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  BDNF, as an axonal growth factor, a pro-survival factor, and a neurotransmitter modulator in the CNS, has high binding activity with tropomyosin receptor kinase B (TrkB). […] The BDNF/TrkB signaling pathway plays a critical role in the regulation of neuronal survival, structural changes, and plasticity. […] Upregulation of BDNF can increase the size of regenerated axons and myelin sheath thickness. […] The mechanism of physical modulation to promote peripheral nerve regeneration. […] The typical strategies developed for physical modulation of peripheral nerve regeneration include ES, mechanical stretching, magnetic stimulation, pulsed ultrasound, and light stimulation. […] Their current mechanism and application in peripheral regeneration are reviewed below. […] Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons.

• #60 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. […] However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. […] Therefore, the basic mechanisms of PNI have not been comprehensively understood. […] After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. […] For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration. […] The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.

• #61 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. […] However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. […] Therefore, the basic mechanisms of PNI have not been comprehensively understood. […] After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. […] For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration. […] The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.

• #62

  https://journals.lww.com/nrronline/fulltext/2022/10000/basic_mechanisms_of_peripheral_nerve_injury_and.15.aspx

  Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. […] However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. Therefore, the basic mechanisms of PNI have not been comprehensively understood. […] Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI, as well as to alleviate neuropathic pain, the specific mechanisms of successful PNI treatment are unclear. […] After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. […] For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.

• #63 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #64

  https://journals.lww.com/nrronline/fulltext/2022/10000/basic_mechanisms_of_peripheral_nerve_injury_and.15.aspx

  The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. […] This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function.

• #65 Analysis of the immune response to sciatic nerve injury identifies efferocytosis as a key mechanism of nerve debridement | eLife

  https://elifesciences.org/articles/60223

  Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6Chigh monocytes infiltrate the nerve first and rapidly give way to Ly6Cnegative inflammation-resolving macrophages. […] In the injured nerve, macrophages eat apoptotic leukocytes, a process called efferocytosis, and thereby promote an anti-inflammatory milieu. […] Thus, carefully orchestrated inflammation resolution in the nerve is required for conditioning-lesion-induced neurorepair. […] Following PNS injury, Schwann cells (SC) reprogram into repair cells and together with MES and nerve-resident macrophages produce chemokines and cytokines to promote entry of hematogenous immune cells. […] Despite recent progress, it remains unclear which cell types in the injured nerve contribute to tissue debridement and there is a paucity in our understanding of the underlying molecular mechanisms.

• #66 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #67 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #68 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #69

  https://journals.lww.com/nrronline/fulltext/2022/10000/basic_mechanisms_of_peripheral_nerve_injury_and.15.aspx

  The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. […] This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function.

• #70 Peripheral nerve injuries | MedLink Neurology

  https://www.medlink.com/articles/peripheral-nerve-injuries

  In injuries that do not completely disrupt the nerve (neuromas-in-continuity) or in nerves that have been surgically reapproximated, there exists the possibility of axonal regeneration. […] The regeneration process requires the restoration of large quantities of axonal lipids and proteins, the synthesis of which occurs in the nerve cell body before being transported down the axon via axoplasmic flow.

• #71 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #72 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #73 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #74 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #75

  https://journals.lww.com/nrronline/fulltext/2022/10000/basic_mechanisms_of_peripheral_nerve_injury_and.15.aspx

  The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. […] This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function.

• #76 Acute Nerve Injury: Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/249621-overview

  The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. […] The fifth mechanism of injury is stretch injury. […] A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. […] A seventh mechanism of injury is cold injury. […] Each of the mechanisms of injury causes specific damage to a nerve. […] Wallerian degeneration occurs in peripheral nerves. […] Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/day. […] Axonal regeneration is guided toward the distal end of the nerve by a gradient of diffusible substances. […] Misdirected axonal buds can result in abnormal nerve connections. […] Motor endplates must be reinnervated within 18 months of trauma for function to be resumed. […] In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium.

• #77 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Peripheral nerve injuries are common conditions with broad ranging groups of symptoms depending on the severity and nerves involved. […] Although much knowledge exists on the mechanisms of injury and regeneration, reliable treatments that ensure full functional recovery are scarce. […] The most severe form of injury is called neurotmesis, which is a full transection of the axons and connective tissue layers wherein complete discontinuity of the nerve is observed. […] Compression injuries are not always captured by the commonly used classification schemes. […] Nonetheless, there is little doubt that the majority of peripheral nerve compressions fall under the general class of neurapraxia, or Grade I nerve injuries, and commonly occur in locations where nerves pass through narrow anatomical openings.

• #78 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Light and electron microscopy shows that normal nerve morphology and neuromuscular junctions are still present in chronic compression injuries. […] However, a degraded, thinner myelin sheath is seen, as evidenced by an increased g ratio and a decreased internodal length. […] There are various proposed mechanisms that are thought to lead to compression injuries. […] The narrowing of openings leads to increased pressure at that site, compressing blood vessels and leading to nerve ischemia. […] Chronic compression injury was once thought of as a milder form of Wallerian degeneration. […] The role of macrophages and their mitogenic factors, like interleukins, in promoting Schwann cell activity has been proposed but is unlikely since Schwann cells are able to proliferate in the absence of macrophages.

• #79 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Light and electron microscopy shows that normal nerve morphology and neuromuscular junctions are still present in chronic compression injuries. […] However, a degraded, thinner myelin sheath is seen, as evidenced by an increased g ratio and a decreased internodal length. […] There are various proposed mechanisms that are thought to lead to compression injuries. […] The narrowing of openings leads to increased pressure at that site, compressing blood vessels and leading to nerve ischemia. […] Chronic compression injury was once thought of as a milder form of Wallerian degeneration. […] The role of macrophages and their mitogenic factors, like interleukins, in promoting Schwann cell activity has been proposed but is unlikely since Schwann cells are able to proliferate in the absence of macrophages.

• #80 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Light and electron microscopy shows that normal nerve morphology and neuromuscular junctions are still present in chronic compression injuries. […] However, a degraded, thinner myelin sheath is seen, as evidenced by an increased g ratio and a decreased internodal length. […] There are various proposed mechanisms that are thought to lead to compression injuries. […] The narrowing of openings leads to increased pressure at that site, compressing blood vessels and leading to nerve ischemia. […] Chronic compression injury was once thought of as a milder form of Wallerian degeneration. […] The role of macrophages and their mitogenic factors, like interleukins, in promoting Schwann cell activity has been proposed but is unlikely since Schwann cells are able to proliferate in the absence of macrophages.

• #81 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Light and electron microscopy shows that normal nerve morphology and neuromuscular junctions are still present in chronic compression injuries. […] However, a degraded, thinner myelin sheath is seen, as evidenced by an increased g ratio and a decreased internodal length. […] There are various proposed mechanisms that are thought to lead to compression injuries. […] The narrowing of openings leads to increased pressure at that site, compressing blood vessels and leading to nerve ischemia. […] Chronic compression injury was once thought of as a milder form of Wallerian degeneration. […] The role of macrophages and their mitogenic factors, like interleukins, in promoting Schwann cell activity has been proposed but is unlikely since Schwann cells are able to proliferate in the absence of macrophages.

• #82 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  Light and electron microscopy shows that normal nerve morphology and neuromuscular junctions are still present in chronic compression injuries. […] However, a degraded, thinner myelin sheath is seen, as evidenced by an increased g ratio and a decreased internodal length. […] There are various proposed mechanisms that are thought to lead to compression injuries. […] The narrowing of openings leads to increased pressure at that site, compressing blood vessels and leading to nerve ischemia. […] Chronic compression injury was once thought of as a milder form of Wallerian degeneration. […] The role of macrophages and their mitogenic factors, like interleukins, in promoting Schwann cell activity has been proposed but is unlikely since Schwann cells are able to proliferate in the absence of macrophages.

• #83 Peripheral Nerve Trauma: Mechanisms of Injury and Recovery

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4408553/

  More recent studies have shown that shear stress alone can induce Schwann cell demyelination, proliferation and re-myelination. […] The examination of these two mechanisms begets the question of why the Schwann cells are chiefly affected and not the neurons themselves. […] When an end-organ becomes denervated, reinnervation can occur in two ways: through collateral branching of intact axons or by regeneration of the injured axon. […] In injuries where 20-30% of the axons are damaged, collateral branching is the primary mechanism of recovery. […] In injuries affecting greater than 90% of the axon population within a nerve, axonal regeneration is the primary means for recovery. […] Failure of any of these processes can contribute to the poor functional outcome commonly observed in patients with peripheral nerve injuries.

• #84 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/timing-of-surgical-intervention-in-peripheral-nerve-injuries-from-gunshot-wounds-management-and-review-of-the-literature/

  Gunshot wounds (GSWs) can result in various peripheral nerve injuries (PNIs), ranging from direct nerve transection to neuropraxia caused by the ballistic shockwave mechanism. […] There is still debate about the optimal treatment timing following peripheral nerve injuries (PNIs) from GSWs. Early intervention may prevent dense scar tissue formation and intraneural edema, leading to improved outcomes. […] The timing of nerve repair must be considered to optimize patient outcomes. Immediate intervention can improve patient recovery by preventing the collapse of endoneurial tubes needed for nerve regeneration, as well as decreasing the level of muscular denervation. […] Furthermore, appropriate timing of intervention is needed, as untreated injured nerves can regenerate in a disorganized process, resulting in neuroma formation.

• #85 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/timing-of-surgical-intervention-in-peripheral-nerve-injuries-from-gunshot-wounds-management-and-review-of-the-literature/

  Gunshot wounds (GSWs) can result in various peripheral nerve injuries (PNIs), ranging from direct nerve transection to neuropraxia caused by the ballistic shockwave mechanism. […] There is still debate about the optimal treatment timing following peripheral nerve injuries (PNIs) from GSWs. Early intervention may prevent dense scar tissue formation and intraneural edema, leading to improved outcomes. […] The timing of nerve repair must be considered to optimize patient outcomes. Immediate intervention can improve patient recovery by preventing the collapse of endoneurial tubes needed for nerve regeneration, as well as decreasing the level of muscular denervation. […] Furthermore, appropriate timing of intervention is needed, as untreated injured nerves can regenerate in a disorganized process, resulting in neuroma formation.

• #86 Iatrogenic peripheral nerve injury: a guide to management for the orthopaedic limb surgeon in: EFORT Open Reviews Volume 6 Issue 8 (2021)

  https://eor.bioscientifica.com/view/journals/eor/6/8/2058-5241.6.200123.xml

  The focus of this review is to raise awareness of iatrogenic peripheral nerve injuries in orthopaedic limb surgery, the importance of regular clinical examination, the role of investigations, timing and nature of interventions and also to provide a guide to when onward referral to a specialist peripheral nerve injury unit is recommended. […] Estimates suggest that between 8% and 25.4% of all peripheral nerve injuries (PNI) may be as a direct response of medical intervention. Orthopaedics is the surgical sub-specialty that is associated with the highest rates of iatrogenic injury to peripheral nerves, reflecting the nature of injury and disease in the axial skeleton and limbs, the surgical proximity to the nerves and the techniques involved in surgical reconstruction. […] Early recognition of a peripheral nerve injury is essential. Prompt and appropriate intervention may prevent further deterioration, reduce the risk of neuropathic pain sensitization and improve the chance of a meaningful recovery for a mixed or motor nerve.

• #87 Iatrogenic peripheral nerve injury: a guide to management for the orthopaedic limb surgeon in: EFORT Open Reviews Volume 6 Issue 8 (2021)

  https://eor.bioscientifica.com/view/journals/eor/6/8/2058-5241.6.200123.xml

  Nerves may be inadvertently injured during trauma surgery due to distorted anatomy, traction applied to a limb, soft tissue retraction, by power tools, instrumentation and from compartment syndrome. Elective orthopaedic surgery has additional risks of joint dislocation for arthroplasty surgery, limb lengthening, thermal injury from cement and direct injury from peripheral nerve blocks. […] The true incidence is unknown, and many cases are diagnosed as neurapraxia with the expectation of a full and timely recovery without the need for intervention. The incorrect assignation of a neurapraxia diagnosis may delay treatment for a higher grade of injury and in addition fails to recognize that a diagnosis of neurapraxia should be made with caution and a commitment to regular clinical review. Untreated, a neurapraxia can deteriorate and result in axonopathy. The failure to promptly diagnose such a nerve injury and instigate treatment may result in further deterioration and expose the clinician to medicolegal challenge.

• #88 The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor | Journal of NeuroEngin

  https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-022-01089-1

  We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). […] The anatomical distribution of PNIs implies a role for mechanical forces as these localizations mirror sites known to be vulnerable to compression and/or traction injury. […] The mechanisms underlying the propensity for PNI in COVID-19 critical illness is difficult to establish, but the anatomical distribution of these injuries implicate mechanical forces such as prolonged pressure against bony prominence leading to axonal injury from local ischemia. […] Given the ongoing COVID-19 pandemic, and risks of new variants causing a resurgence of hospital admissions, further attention should be paid to the long-term sequela including PNIs.

• #89 The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor | Journal of NeuroEngin

  https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-022-01089-1

  We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). […] The anatomical distribution of PNIs implies a role for mechanical forces as these localizations mirror sites known to be vulnerable to compression and/or traction injury. […] The mechanisms underlying the propensity for PNI in COVID-19 critical illness is difficult to establish, but the anatomical distribution of these injuries implicate mechanical forces such as prolonged pressure against bony prominence leading to axonal injury from local ischemia. […] Given the ongoing COVID-19 pandemic, and risks of new variants causing a resurgence of hospital admissions, further attention should be paid to the long-term sequela including PNIs.

• #90 Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9083151/

  This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. […] The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. […] After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. […] A slow speed of axon regeneration leads to low nerve regeneration. […] Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. […] From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. […] The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration.

• #91

  https://journals.lww.com/nrronline/fulltext/2022/10000/basic_mechanisms_of_peripheral_nerve_injury_and.15.aspx

  The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration. […] Findings from the included studies confirm that after PNI, a series of physiological and pathological changes occur in the spinal cord, injury site, and target organs, leading to dysfunction. […] Electrical stimulation may address the pathophysiological changes mentioned above, thus promoting nerve regeneration and ameliorating dysfunction.

• #92 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  The application of ES can alter the microenvironment of the site of PNI and promote the polarization of macrophages towards reparative macrophages by changing chemokine signals, which ultimately eliminates the inflammatory reactions and promotes peripheral nerve regeneration. […] Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. […] Ultrasound can activate the superficial and deep neural structures and modulate the neuronal activity in humans, leading to different sensations of heat, touch and pain. […] The levels of pro-inflammatory cytokines TNF-, IL-1, and IL-17 in the sciatic nerve were significantly reduced, while the levels of anti-inflammatory cytokines IL-4 and IL-10 were significantly increased. […] The nervous system is under a dynamic and continuous stimulus of mechanical stretching, which is also the direct effect of physical exercise and movement rehabilitation.

• #93 Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery

  https://www.ijbs.com/v16p0116.htm

  The basic limitations of present therapies are slow nerve regeneration and insufficient filling of large gaps. To overcome these limitations, cell-based therapy was designed to provide supportive cells to the lesion site with the aim to accelerate nerve regeneration which could replace the use of all other available surgical therapies. Most extensively studied therapeutic models are Schwann cells (SCs), but remarkable improvements were also achieved with different types of stem cells as well. […] The ideal cells used for neural regeneration should have the following properties such as easy harvesting, no requirement of immunosuppression, able to integrate to the injury site and non-tumorigenic. The success of a cell-based therapy depends on the transplanted cell’s ability to differentiate into Schwann-like cells, to release neurotrophic growth factors and to induce myelination of axons.

• #94 Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery

  https://www.ijbs.com/v16p0116.htm

  The basic limitations of present therapies are slow nerve regeneration and insufficient filling of large gaps. To overcome these limitations, cell-based therapy was designed to provide supportive cells to the lesion site with the aim to accelerate nerve regeneration which could replace the use of all other available surgical therapies. Most extensively studied therapeutic models are Schwann cells (SCs), but remarkable improvements were also achieved with different types of stem cells as well. […] The ideal cells used for neural regeneration should have the following properties such as easy harvesting, no requirement of immunosuppression, able to integrate to the injury site and non-tumorigenic. The success of a cell-based therapy depends on the transplanted cell’s ability to differentiate into Schwann-like cells, to release neurotrophic growth factors and to induce myelination of axons.

• #95 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  The application of ES can alter the microenvironment of the site of PNI and promote the polarization of macrophages towards reparative macrophages by changing chemokine signals, which ultimately eliminates the inflammatory reactions and promotes peripheral nerve regeneration. […] Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. […] Ultrasound can activate the superficial and deep neural structures and modulate the neuronal activity in humans, leading to different sensations of heat, touch and pain. […] The levels of pro-inflammatory cytokines TNF-, IL-1, and IL-17 in the sciatic nerve were significantly reduced, while the levels of anti-inflammatory cytokines IL-4 and IL-10 were significantly increased. […] The nervous system is under a dynamic and continuous stimulus of mechanical stretching, which is also the direct effect of physical exercise and movement rehabilitation.

• #96 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  The application of ES can alter the microenvironment of the site of PNI and promote the polarization of macrophages towards reparative macrophages by changing chemokine signals, which ultimately eliminates the inflammatory reactions and promotes peripheral nerve regeneration. […] Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. […] Ultrasound can activate the superficial and deep neural structures and modulate the neuronal activity in humans, leading to different sensations of heat, touch and pain. […] The levels of pro-inflammatory cytokines TNF-, IL-1, and IL-17 in the sciatic nerve were significantly reduced, while the levels of anti-inflammatory cytokines IL-4 and IL-10 were significantly increased. […] The nervous system is under a dynamic and continuous stimulus of mechanical stretching, which is also the direct effect of physical exercise and movement rehabilitation.

• #97 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  The application of ES can alter the microenvironment of the site of PNI and promote the polarization of macrophages towards reparative macrophages by changing chemokine signals, which ultimately eliminates the inflammatory reactions and promotes peripheral nerve regeneration. […] Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. […] Ultrasound can activate the superficial and deep neural structures and modulate the neuronal activity in humans, leading to different sensations of heat, touch and pain. […] The levels of pro-inflammatory cytokines TNF-, IL-1, and IL-17 in the sciatic nerve were significantly reduced, while the levels of anti-inflammatory cytokines IL-4 and IL-10 were significantly increased. […] The nervous system is under a dynamic and continuous stimulus of mechanical stretching, which is also the direct effect of physical exercise and movement rehabilitation.

• #98 Physical modulation and peripheral nerve regeneration: a literature review | Cell Regeneration | Full Text

  https://cellregeneration.springeropen.com/articles/10.1186/s13619-024-00215-9

  Mechanosensitive ion channels represent a family of pore-forming proteins crucial for detecting intra- and extracellular mechanical stimulus (e.g., pressure and stretch). […] The enhancement of energy metabolism of SCs by mechanical stretching may be applied to explain the mechanism of therapeutic effects of physical exercise and mechanical stretching on peripheral nerve regeneration. […] Physical modulation employing electric, light, ultrasound, magnetic stimulus, and mechanical stretching has displayed powerful potential and promising application in the field of peripheral nerve regeneration.

• #99 Peripheral Nerve Injuries: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/1270360-overview

  Peripheral nerve injury may result in demyelination, axonal degeneration, or both. Clinically, both demyelination and axonal degeneration result in disruption of sensory function, motor function, or both in the injured nerve. Depending on the severity and degree of nerve injury, recovery of function occurs with remyelination and with axonal regeneration and reinnervation of the sensory receptors, motor end plates, or both. […] The future in peripheral nerve injuries lies in maximizing motor and sensory recovery after nerve injury. Strategies to maintain the neuromuscular junction are important for permitting muscle reinnervation after prolonged muscle denervation, as well as decreasing injury to the cell body. […] In traumatic nerve injury with large nerve gaps, nerve allografts have been described. However, because of the morbidity associated with immunosuppression, the use of the nerve allograft has been stringently limited to otherwise unreconstructable injuries. Investigations to decrease the antigenicity of the allograft or induce tolerance to the nerve allograft are ongoing, and success in these investigations will permit the use of nerve allografts without immunosuppression.

• #100 Peripheral Nerve Injuries: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/1270360-overview

  Peripheral nerve injury may result in demyelination, axonal degeneration, or both. Clinically, both demyelination and axonal degeneration result in disruption of sensory function, motor function, or both in the injured nerve. Depending on the severity and degree of nerve injury, recovery of function occurs with remyelination and with axonal regeneration and reinnervation of the sensory receptors, motor end plates, or both. […] The future in peripheral nerve injuries lies in maximizing motor and sensory recovery after nerve injury. Strategies to maintain the neuromuscular junction are important for permitting muscle reinnervation after prolonged muscle denervation, as well as decreasing injury to the cell body. […] In traumatic nerve injury with large nerve gaps, nerve allografts have been described. However, because of the morbidity associated with immunosuppression, the use of the nerve allograft has been stringently limited to otherwise unreconstructable injuries. Investigations to decrease the antigenicity of the allograft or induce tolerance to the nerve allograft are ongoing, and success in these investigations will permit the use of nerve allografts without immunosuppression.

• #101 The Treatment of Peripheral Nerve Injuries (09.08.2024)

  https://di.aerzteblatt.de/int/archive/article/240616/The-treatment-of-peripheral-nerve-injuries

  If a nerve shows clinical signs of dysfunction and has an open injury along its course, one can assume in the first instance that it is involved, and immediate exploration shall be undertaken. […] The role of the distal nerve transfer […] Nerve transfer enables the reinnervation of the affected musculature by transferring sacrificable motor fascicles from a healthy donor nerve near the target muscle to the motor branches of the damaged nerve, thereby converting a proximal lesion into a distal lesion. […] The advantages of this method include a shorter reinnervation distance and reduced reinnervation times, while at the same time clearly defining which donor motor (more rarely, sensory) fascicles are assigned to which recipient fascicles. Nerve transfers should be used when nerve reconstruction is not feasible or unlikely to succeed.

• #102 The Treatment of Peripheral Nerve Injuries (09.08.2024)

  https://di.aerzteblatt.de/int/archive/article/240616/The-treatment-of-peripheral-nerve-injuries

  The quality of the evidence is greatly reduced by the quality of the included studies, the considerable variability in follow-up times, and the widely varying group sizes. Therefore, a trend towards better outcomes following nerve transfer can only be reported for the reconstruction of elbow flexion.

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