Materiały źródłowe

• #1 Pathogenesis and pathophysiology of bacterial meningitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-and-pathophysiology-of-bacterial-meningitis

  Pathogenesis and pathophysiology of bacterial meningitis involve a complex interplay between virulence factors of the pathogens and the host immune response. […] Bacterial meningitis develops when virulence factors of the pathogen overcome host defense mechanisms.

• #2 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #3 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #4 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  In most cases, meningitis is caused by an infectious agent that has colonized or established a localized infection in various parts of the body such as the skin, nose and throat, respiratory tract, gastrointestinal tract, or genitourinary tract. The organism is able to invade the submucosa at these sites by bypassing the host’s defenses (eg, physical barriers, local immunity, and phagocytes, or macrophages). […] An infectious agent (such as a bacterium, virus, fungus, or parasite) can access the CNS and cause meningeal disease through any of the following three major pathways: Invasion of the bloodstream (eg, bacteremia, viremia, fungemia, or parasitemia) leading to subsequent hematogenous seeding of the CNS; Utilizing a retrograde neuronal pathway (eg, olfactory and peripheral nerves), as seen with organisms like Naegleria fowleri or Gnathostoma spinigerum; Direct contiguous spread through methods such as sinusitis, otitis media, congenital malformations, trauma, or direct inoculation during intracranial manipulation.

• #5 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  In most cases, meningitis is caused by an infectious agent that has colonized or established a localized infection in various parts of the body such as the skin, nose and throat, respiratory tract, gastrointestinal tract, or genitourinary tract. The organism is able to invade the submucosa at these sites by bypassing the host’s defenses (eg, physical barriers, local immunity, and phagocytes, or macrophages). […] An infectious agent (such as a bacterium, virus, fungus, or parasite) can access the CNS and cause meningeal disease through any of the following three major pathways: Invasion of the bloodstream (eg, bacteremia, viremia, fungemia, or parasitemia) leading to subsequent hematogenous seeding of the CNS; Utilizing a retrograde neuronal pathway (eg, olfactory and peripheral nerves), as seen with organisms like Naegleria fowleri or Gnathostoma spinigerum; Direct contiguous spread through methods such as sinusitis, otitis media, congenital malformations, trauma, or direct inoculation during intracranial manipulation.

• #6 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  In most cases, meningitis is caused by an infectious agent that has colonized or established a localized infection in various parts of the body such as the skin, nose and throat, respiratory tract, gastrointestinal tract, or genitourinary tract. The organism is able to invade the submucosa at these sites by bypassing the host’s defenses (eg, physical barriers, local immunity, and phagocytes, or macrophages). […] An infectious agent (such as a bacterium, virus, fungus, or parasite) can access the CNS and cause meningeal disease through any of the following three major pathways: Invasion of the bloodstream (eg, bacteremia, viremia, fungemia, or parasitemia) leading to subsequent hematogenous seeding of the CNS; Utilizing a retrograde neuronal pathway (eg, olfactory and peripheral nerves), as seen with organisms like Naegleria fowleri or Gnathostoma spinigerum; Direct contiguous spread through methods such as sinusitis, otitis media, congenital malformations, trauma, or direct inoculation during intracranial manipulation.

• #7 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  The most common mode of spread for many pathogens is through invasion of the bloodstream and subsequent seeding. This pathway is characteristic of meningococcal, cryptococcal, syphilitic, and pneumococcal meningitis. […] The protective barrier created by the meninges shields the brain from the immune system, but in cases of meningitis, this defense can be breached, enabling bacteria to infiltrate and cause infection. The body’s effort to combat the infection may exacerbate the situation by causing blood vessels to become leaky, leading to brain swelling and diminished blood flow. Severe bacterial meningitis can break through the pial barrier, causing extensive brain damage. […] The sustained inflammatory response in meningitis is fueled by factors like bacterial replication, increased inflammatory cells, and disruptions in membrane transport, resulting in alterations in the composition of cerebrospinal fluid, including changes in cell count, pH, lactate, protein, and glucose levels.

• #8 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #9

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  In particular, the excessive inflammatory response of neutrophils (PMNs) has been associated with increased CNS injury. […] Pathogens causing meningitis often colonize mucosal surfaces and show similar patterns of disease progression. […] Many bacteria bind to extracellular matrix proteins, e.g., laminin, collagen or fibronectin, to facilitate initial attachment preceding invasion. […] A hallmark of many bacteria infecting the CNS is their ability to survive in the blood stream by either avoiding or protecting against phagocytosis. […] However, sustained bacteremia is not always a prerequisite for bacterial entrance to the CNS, since meningitis can also be caused by direct invasion from neighboring infected tissues. […] Nevertheless, all bacteria have to breach certain barriers, such as the BBB and blood-CSF barrier (B-CSFB), to get access to the brain.

• #10

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  In particular, the excessive inflammatory response of neutrophils (PMNs) has been associated with increased CNS injury. […] Pathogens causing meningitis often colonize mucosal surfaces and show similar patterns of disease progression. […] Many bacteria bind to extracellular matrix proteins, e.g., laminin, collagen or fibronectin, to facilitate initial attachment preceding invasion. […] A hallmark of many bacteria infecting the CNS is their ability to survive in the blood stream by either avoiding or protecting against phagocytosis. […] However, sustained bacteremia is not always a prerequisite for bacterial entrance to the CNS, since meningitis can also be caused by direct invasion from neighboring infected tissues. […] Nevertheless, all bacteria have to breach certain barriers, such as the BBB and blood-CSF barrier (B-CSFB), to get access to the brain.

• #11 Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

  https://www.mdpi.com/1422-0067/20/21/5393

  To facilitate adhesion and invasion of the barriers protecting the brain, a threshold level of bacteremia has been shown to be required, which is correlated with the severity of infection and likeliness of developing meningitis. However, direct invasion from neighboring infected tissues can occur as well. […] Bacterial adhesion to host cell surfaces is a complex process. It involves multiple adhesion molecules of the pathogen interacting with a variety of target receptors. These interactions, which can involve several adhesins of one microbe, can occur in a sequential manner. Hereby, the initial interactions can trigger the expression of further host receptors, which are then targeted by other bacterial adhesins. […] Many pathogens have been shown to bind to extracellular matrix proteins to facilitate initial attachment to the host cells. Furthermore, binding of bacterial adhesins to specific host cell receptors can in turn induce different signal transduction pathways, resulting in tight attachment or internalization of the bacteria into the host cells.

• #12 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Meningitis-Mechanism.aspx

  The bacteria or infective organism spreads through the blood. They reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. The infection begins in one part of the body e.g. throat or lungs and spreads to the brain. […] Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood-brain barrier is vulnerable such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults. […] This leads to activation of the immune system that leads to swelling of the meninges to stop the spread of the infection. This swelling damages the brain and the nervous system.

• #13 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Meningitis-Mechanism.aspx

  The bacteria or infective organism spreads through the blood. They reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. The infection begins in one part of the body e.g. throat or lungs and spreads to the brain. […] Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood-brain barrier is vulnerable such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults. […] This leads to activation of the immune system that leads to swelling of the meninges to stop the spread of the infection. This swelling damages the brain and the nervous system.

• #14 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #15

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  In particular, the excessive inflammatory response of neutrophils (PMNs) has been associated with increased CNS injury. […] Pathogens causing meningitis often colonize mucosal surfaces and show similar patterns of disease progression. […] Many bacteria bind to extracellular matrix proteins, e.g., laminin, collagen or fibronectin, to facilitate initial attachment preceding invasion. […] A hallmark of many bacteria infecting the CNS is their ability to survive in the blood stream by either avoiding or protecting against phagocytosis. […] However, sustained bacteremia is not always a prerequisite for bacterial entrance to the CNS, since meningitis can also be caused by direct invasion from neighboring infected tissues. […] Nevertheless, all bacteria have to breach certain barriers, such as the BBB and blood-CSF barrier (B-CSFB), to get access to the brain.

• #16 Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

  https://www.mdpi.com/1422-0067/20/21/5393

  The use of pili or fibrils for invasion of HBMECs was observed for a multitude of meningitis-causing pathogens, making them highly important virulence factors for invasion of the CNS. […] Meningitis-causing pathogens most commonly cross host barriers in a transcellular or paracellular manner. These processes are associated with protein interactions between pathogens and the host’s cells. Transcellular traversal is characterized by pathogens crossing the barrier cells without evidence of TJ disruption or traversal between cells. This is accomplished by intracellular invasion of the barrier cells and exploitation of signaling pathways. Paracellular traversal, on the other hand, involves penetration of pathogens between the host’s cells and can occur with and without permanent disruption of TJs. Furthermore, the release of bacterial toxins can lead to disruption of barrier function and promote paracellular traversal.

• #17 Elucidating the pathogenic mechanism of meningococcal meningitis | Institut Pasteur

  https://www.pasteur.fr/en/elucidating-pathogenic-mechanism-meningococcal-meningitis?language=fr

  Neisseria meningitidis, also called meningococcus, is a bacterium responsible for meningitis and septicemia. […] This bacterium, which is naturally present in humans in the nasopharynx, is pathogenic if it reaches the blood stream. […] When the bacterium Neisseria meningitidis multiplies in the blood, it interacts with the endothelial cells that line the inside of blood vessels and adheres to their walls. […] In the brain, when meningococci adhere to the vessels they can pass through the blood-brain barrier, and cause meningitis when they invade the meninges. […] Teams of researchers have deciphered how Neisseria meningitidis adheres to blood vessels, a step that underpins the bacterium’s pathogenicity. […] In blood vessels they have identified receptor CD147, whose expression is essential for initial meningococcal adherence to endothelial cells.

• #18 Elucidating the pathogenic mechanism of meningococcal meningitis | Institut Pasteur

  https://www.pasteur.fr/en/elucidating-pathogenic-mechanism-meningococcal-meningitis?language=fr

  If this receptor is absent, N. meningitidis cannot implant in blood vessels and colonize them. […] The researchers have determined that two pilins, PilE and PilV, interact directly with the CD147 receptor. […] Without them, meningococci cannot adhere to endothelial cells. […] These mice were then infected by meningococci naturally having pilins PilE and PilV, or meningococci in which the expression of these pilins had been artificially suppressed. […] The human blood vessels were only infected by meningococci displaying PilE and PilV, which confirms that these two pilins are essential to the bacterial colonization process. […] The researchers also showed in an ex vivo infection model that cerebral vessels and meninges, particularly rich in CD147 receptors, allow colonization by meningococci, unlike other parts of the brain. […] The scientists now wish to develop a new type of vaccine that would block the interaction between N. meningitidis and the CD147 receptors, thereby stopping the bacterium from colonizing the vessels.

• #19

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  Once the pathogen has reached the brain, bacteria (or bacterial components) are recognized by resident immune cells, such as microglia and astrocytes, leading to their activation. […] The entire symptom complex of meningitis can be triggered in the absence of live bacteria, when only components of the bacterial cell wall are intracisternally inoculated into animals. […] The most important PRRs responsible for the detection of the pneumococcus in the CNS are members of the Toll-like receptor (TLR) family (TLR2, TLR4 and TLR9) and NOD2 that belongs to the family of NOD-like receptors (NLRs). […] Engagement of the inflammatory response activates various signaling cascades resulting in the production of pro-inflammatory mediators that orchestrate an efficient immune response. […] The acute inflammatory response is compartmentalized within the subarachnoid space and is characterized by the release of tumor necrosis factor (TNF-), IL-1, IL-6, IL-8, MCP-1, MIP- and G-CSF.

• #20 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Meningitis-Mechanism.aspx

  The organism may also affect the cerebrospinal fluid (CSF). This adds to the injury and there is increased pressure on the brain and on the skull. This is called raised intracranial pressure. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses. […] With the inflammation, the immune system identifies the bacteria by its cell wall. The immune cells of the brain (astrocytes and microglia), respond by releasing large amounts of cytokines that are hormone-like mediators that recruit other immune cells. This stimulates other tissues to participate in an immune response. […] The blood-brain barrier becomes more permeable, leading to „vasogenic” cerebral edema (swelling of the brain due to fluid leakage from blood vessels). The blood vessels are also inflamed leading to cerebral vasculitis which leads to a decreased blood flow another type of edema, „cytotoxic” edema.

• #21

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  Once the pathogen has reached the brain, bacteria (or bacterial components) are recognized by resident immune cells, such as microglia and astrocytes, leading to their activation. […] The entire symptom complex of meningitis can be triggered in the absence of live bacteria, when only components of the bacterial cell wall are intracisternally inoculated into animals. […] The most important PRRs responsible for the detection of the pneumococcus in the CNS are members of the Toll-like receptor (TLR) family (TLR2, TLR4 and TLR9) and NOD2 that belongs to the family of NOD-like receptors (NLRs). […] Engagement of the inflammatory response activates various signaling cascades resulting in the production of pro-inflammatory mediators that orchestrate an efficient immune response. […] The acute inflammatory response is compartmentalized within the subarachnoid space and is characterized by the release of tumor necrosis factor (TNF-), IL-1, IL-6, IL-8, MCP-1, MIP- and G-CSF.

• #22

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  Once the pathogen has reached the brain, bacteria (or bacterial components) are recognized by resident immune cells, such as microglia and astrocytes, leading to their activation. […] The entire symptom complex of meningitis can be triggered in the absence of live bacteria, when only components of the bacterial cell wall are intracisternally inoculated into animals. […] The most important PRRs responsible for the detection of the pneumococcus in the CNS are members of the Toll-like receptor (TLR) family (TLR2, TLR4 and TLR9) and NOD2 that belongs to the family of NOD-like receptors (NLRs). […] Engagement of the inflammatory response activates various signaling cascades resulting in the production of pro-inflammatory mediators that orchestrate an efficient immune response. […] The acute inflammatory response is compartmentalized within the subarachnoid space and is characterized by the release of tumor necrosis factor (TNF-), IL-1, IL-6, IL-8, MCP-1, MIP- and G-CSF.

• #23

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  Once the pathogen has reached the brain, bacteria (or bacterial components) are recognized by resident immune cells, such as microglia and astrocytes, leading to their activation. […] The entire symptom complex of meningitis can be triggered in the absence of live bacteria, when only components of the bacterial cell wall are intracisternally inoculated into animals. […] The most important PRRs responsible for the detection of the pneumococcus in the CNS are members of the Toll-like receptor (TLR) family (TLR2, TLR4 and TLR9) and NOD2 that belongs to the family of NOD-like receptors (NLRs). […] Engagement of the inflammatory response activates various signaling cascades resulting in the production of pro-inflammatory mediators that orchestrate an efficient immune response. […] The acute inflammatory response is compartmentalized within the subarachnoid space and is characterized by the release of tumor necrosis factor (TNF-), IL-1, IL-6, IL-8, MCP-1, MIP- and G-CSF.

• #24 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #25 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #26 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Meningitis-Mechanism.aspx

  The organism may also affect the cerebrospinal fluid (CSF). This adds to the injury and there is increased pressure on the brain and on the skull. This is called raised intracranial pressure. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses. […] With the inflammation, the immune system identifies the bacteria by its cell wall. The immune cells of the brain (astrocytes and microglia), respond by releasing large amounts of cytokines that are hormone-like mediators that recruit other immune cells. This stimulates other tissues to participate in an immune response. […] The blood-brain barrier becomes more permeable, leading to „vasogenic” cerebral edema (swelling of the brain due to fluid leakage from blood vessels). The blood vessels are also inflamed leading to cerebral vasculitis which leads to a decreased blood flow another type of edema, „cytotoxic” edema.

• #27 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  Exudates spread throughout the cerebrospinal fluid, primarily affecting the basal cisterns, leading to cranial nerve damage (such as cranial nerve VIII, which can result in hearing loss), blockage of CSF flow (resulting in obstructive hydrocephalus), and triggering of vasculitis and thrombophlebitis (resulting in localized brain ischemia). […] Meningitis can lead to increased intracranial pressure (ICP) due to various factors such as interstitial edema, cytotoxic edema, and vasogenic edema. This can result from mechanisms like obstructed CSF flow, toxic factors released by bacteria and neutrophils, and increased permeability of the blood-brain barrier. […] The influx of plasma components into the subarachnoid space and impaired venous outflow contribute to increased cerebrospinal fluid (CSF) viscosity, leading to interstitial edema. Bacterial byproducts, activated cells, and neutrophils lead to cytotoxic edema.

• #28 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  Advancements in understanding the pathophysiology of meningitis have shed light on the crucial roles of various cytokines (eg, tumor necrosis factor alpha [TNF-] and interleukin [IL]-1), chemokines (IL-8), and proinflammatory molecules in pleocytosis and neuronal damage during bacterial meningitis episodes. […] Patients with bacterial meningitis typically exhibit heightened levels of cytokines such as TNF-, IL-1, IL-6, and IL-8 in their CSF. These molecules are believed to play key roles in triggering the inflammatory cascade in meningitis through interactions with pattern-recognition receptors like Toll-like receptors (TLRs). […] In cases of bacterial meningitis, the inflammatory response triggers the recruitment of an excessive number of neutrophils to the subarachnoid space. These activated neutrophils release harmful substances such as oxidants and metalloproteins, which can damage brain tissue.

• #29 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  Advancements in understanding the pathophysiology of meningitis have shed light on the crucial roles of various cytokines (eg, tumor necrosis factor alpha [TNF-] and interleukin [IL]-1), chemokines (IL-8), and proinflammatory molecules in pleocytosis and neuronal damage during bacterial meningitis episodes. […] Patients with bacterial meningitis typically exhibit heightened levels of cytokines such as TNF-, IL-1, IL-6, and IL-8 in their CSF. These molecules are believed to play key roles in triggering the inflammatory cascade in meningitis through interactions with pattern-recognition receptors like Toll-like receptors (TLRs). […] In cases of bacterial meningitis, the inflammatory response triggers the recruitment of an excessive number of neutrophils to the subarachnoid space. These activated neutrophils release harmful substances such as oxidants and metalloproteins, which can damage brain tissue.

• #30

  https://link.springer.com/article/10.1007/s00401-015-1531-z

  In particular, the excessive inflammatory response of neutrophils (PMNs) has been associated with increased CNS injury. […] Pathogens causing meningitis often colonize mucosal surfaces and show similar patterns of disease progression. […] Many bacteria bind to extracellular matrix proteins, e.g., laminin, collagen or fibronectin, to facilitate initial attachment preceding invasion. […] A hallmark of many bacteria infecting the CNS is their ability to survive in the blood stream by either avoiding or protecting against phagocytosis. […] However, sustained bacteremia is not always a prerequisite for bacterial entrance to the CNS, since meningitis can also be caused by direct invasion from neighboring infected tissues. […] Nevertheless, all bacteria have to breach certain barriers, such as the BBB and blood-CSF barrier (B-CSFB), to get access to the brain.

• #31 SciELO Brazil – Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

  https://www.scielo.br/j/anp/a/dMF4mFGHXwjTXSYpR3hnBwp/

  Many brain cells such as astrocytes, glial cells, endothelial cells, ependymal cells, and resident macrophages can produce cytokines and pro-inflammatory molecules in response to bacterial replication and its components. […] The release of large amounts of reactive nitrogen species (RNS) and reactive oxygen species (ROS) had been documented in patient’s populations, likewise, in animal model by pneumococcal meningitis and might contribute to the development of neuronal damage. […] The neuronal damage is caused by the strong inflammatory reaction and direct effects of the microorganism. Significant injury during bacterial meningitis arises from mechanisms of neuronal apoptosis, particularly in the hippocampus; in autopsies cases of bacterial meningitis were found apoptosis of neurons in the dentate gyrus. […] The mortality of S. pneumoniae is (16-37%), N. meningitidis (5%), Haemophilus influenzae (3%). This maintenance of mortality is explained by inflammation in the subarachnoid space caused by the generation of bacterial cell wall components in CSF during treatment of meningitis with antibiotics.

• #32 SciELO Brazil – Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

  https://www.scielo.br/j/anp/a/dMF4mFGHXwjTXSYpR3hnBwp/

  Many brain cells such as astrocytes, glial cells, endothelial cells, ependymal cells, and resident macrophages can produce cytokines and pro-inflammatory molecules in response to bacterial replication and its components. […] The release of large amounts of reactive nitrogen species (RNS) and reactive oxygen species (ROS) had been documented in patient’s populations, likewise, in animal model by pneumococcal meningitis and might contribute to the development of neuronal damage. […] The neuronal damage is caused by the strong inflammatory reaction and direct effects of the microorganism. Significant injury during bacterial meningitis arises from mechanisms of neuronal apoptosis, particularly in the hippocampus; in autopsies cases of bacterial meningitis were found apoptosis of neurons in the dentate gyrus. […] The mortality of S. pneumoniae is (16-37%), N. meningitidis (5%), Haemophilus influenzae (3%). This maintenance of mortality is explained by inflammation in the subarachnoid space caused by the generation of bacterial cell wall components in CSF during treatment of meningitis with antibiotics.

• #33 Meningitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/232915-overview

  Exudates spread throughout the cerebrospinal fluid, primarily affecting the basal cisterns, leading to cranial nerve damage (such as cranial nerve VIII, which can result in hearing loss), blockage of CSF flow (resulting in obstructive hydrocephalus), and triggering of vasculitis and thrombophlebitis (resulting in localized brain ischemia). […] Meningitis can lead to increased intracranial pressure (ICP) due to various factors such as interstitial edema, cytotoxic edema, and vasogenic edema. This can result from mechanisms like obstructed CSF flow, toxic factors released by bacteria and neutrophils, and increased permeability of the blood-brain barrier. […] The influx of plasma components into the subarachnoid space and impaired venous outflow contribute to increased cerebrospinal fluid (CSF) viscosity, leading to interstitial edema. Bacterial byproducts, activated cells, and neutrophils lead to cytotoxic edema.

• #34 New insights in the mechanisms of bacterial brain invasion during meningitis | Karolinska Institutet

  https://news.ki.se/new-insights-in-the-mechanisms-of-bacterial-brain-invasion-during-meningitis

  We shed light into how one single amino acid substitution can dramatically affect the toxic power of PLY, says Federico Iovino, Associate Professor and research group leader at the Department of Neuroscience. […] We have observed that all regions of the brain are equally affected by pneumococcal infection in an experimental meningitis in vivo model and, furthermore, that neurogenesis is severely affected during meningitis pathogenesis, says Kristine Farmen, PhD student in Federico Iovinos research group at the Department of Neuroscience and first author of this second study. […] The findings support the real scenario of meningitis in society, in fact the different brain regions, equally affected by bacterial invasion, control different body functions, and this corresponds to the incredible variety of neurological sequelae experienced by meningitis survivors, says Federico Iovino, last author and principal investigator of the study.

• #35 New insights in the mechanisms of bacterial brain invasion during meningitis | Karolinska Institutet

  https://news.ki.se/new-insights-in-the-mechanisms-of-bacterial-brain-invasion-during-meningitis

  Bacterial meningitis is a devastating infectious disease because, even when cured, most survivors live with permanent neurological disabilities such as motor impairment, cognitive delay, hearing and vision loss, seizures, and psychiatric disorders, due to neuronal damage caused by the infection. Researchers at Karolinska Institutet have now revealed new insights into the mechanisms of bacterial brain invasion and neuronal damage during bacterial meningitis. […] The pneumococcus produces and releases pneumolysin (PLY), which is one of the major weapons used by the bacteria to damage cells. […] We discovered that Streptococcus pneumoniae, isolated from meningitis patients, release a variant of PLY which differs from only one single amino acid compared to the NCBI PLY-reference Streptococcus pneumoniae laboratory strain D39. This single amino acid substitution significantly enhances the capability of PLY to damage neurons, says Simona Serra, PhD student in Federico Iovinos research group at the Department of Neuroscience and first author of the study.

• #36 Elucidating the pathogenic mechanism of meningococcal meningitis | Institut Pasteur

  https://www.pasteur.fr/en/elucidating-pathogenic-mechanism-meningococcal-meningitis?language=fr

  If this receptor is absent, N. meningitidis cannot implant in blood vessels and colonize them. […] The researchers have determined that two pilins, PilE and PilV, interact directly with the CD147 receptor. […] Without them, meningococci cannot adhere to endothelial cells. […] These mice were then infected by meningococci naturally having pilins PilE and PilV, or meningococci in which the expression of these pilins had been artificially suppressed. […] The human blood vessels were only infected by meningococci displaying PilE and PilV, which confirms that these two pilins are essential to the bacterial colonization process. […] The researchers also showed in an ex vivo infection model that cerebral vessels and meninges, particularly rich in CD147 receptors, allow colonization by meningococci, unlike other parts of the brain. […] The scientists now wish to develop a new type of vaccine that would block the interaction between N. meningitidis and the CD147 receptors, thereby stopping the bacterium from colonizing the vessels.

• #37 Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment

  https://www.mdpi.com/2077-0383/9/9/2962

  Tuberculosis (TB) is the most prevalent infectious disease in the world. […] Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. […] TBM is characterized as a severe manifestation of TB and usually requires emergent intervention, due to the quick hematogenous dissemination of the tuberculosis bacillus. […] During hematogenous dissemination, mycobacteria may be deposited adjacent to the ventricles or subarachnoid space, leading to granuloma formation at those sites of deposition. […] TBM occurs when subependymal or subpial tubercles, also known as “rich foci” seed during bacillemia of primary infection or disseminated disease. […] This rupture of the granuloma into the subarachnoid space leads to an intense inflammatory response, which eventually causes meningitis.

• #38 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #39

  https://www.who.int/news-room/fact-sheets/detail/meningitis

  Meningitis is the inflammation of the tissues surrounding the brain and spinal cord. It can be infectious or non-infectious in origin, can be associated with high risk of death and long-term complications, and requires urgent medical care. […] Bacterial meningitis is the most serious type of meningitis. It is a severe, life-threatening condition that can often lead to long-term adverse health consequences. There are four main causes of acute bacterial meningitis: Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae (group B streptococcus). […] These bacteria are responsible for more than half of the deaths from meningitis globally and can cause other severe diseases like sepsis and pneumonia. […] Carriage of these organisms is usually harmless and contributes to building up immunity against infection, but the bacteria occasionally invade the body, causing meningitis, sepsis and other forms of invasive disease.

• #40

  https://www.who.int/news-room/fact-sheets/detail/meningitis

  Meningitis is the inflammation of the tissues surrounding the brain and spinal cord. It can be infectious or non-infectious in origin, can be associated with high risk of death and long-term complications, and requires urgent medical care. […] Bacterial meningitis is the most serious type of meningitis. It is a severe, life-threatening condition that can often lead to long-term adverse health consequences. There are four main causes of acute bacterial meningitis: Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae (group B streptococcus). […] These bacteria are responsible for more than half of the deaths from meningitis globally and can cause other severe diseases like sepsis and pneumonia. […] Carriage of these organisms is usually harmless and contributes to building up immunity against infection, but the bacteria occasionally invade the body, causing meningitis, sepsis and other forms of invasive disease.

• #41

  https://www.who.int/news-room/fact-sheets/detail/meningitis

  Meningitis is the inflammation of the tissues surrounding the brain and spinal cord. It can be infectious or non-infectious in origin, can be associated with high risk of death and long-term complications, and requires urgent medical care. […] Bacterial meningitis is the most serious type of meningitis. It is a severe, life-threatening condition that can often lead to long-term adverse health consequences. There are four main causes of acute bacterial meningitis: Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae (group B streptococcus). […] These bacteria are responsible for more than half of the deaths from meningitis globally and can cause other severe diseases like sepsis and pneumonia. […] Carriage of these organisms is usually harmless and contributes to building up immunity against infection, but the bacteria occasionally invade the body, causing meningitis, sepsis and other forms of invasive disease.

• #42

  https://www.who.int/news-room/fact-sheets/detail/meningitis

  One in 5 people surviving an episode of bacterial meningitis may have long lasting after-effects. These after-effects include hearing loss, seizures, limb weakness, difficulties with vision, speech, language, memory and communication, as well as scarring and limb amputations after sepsis. […] Antibiotic treatment should be started as soon as possible when bacterial meningitis is suspected. The first dose of antibiotic treatment should not be delayed until the results of the lumbar puncture are available. The choice of antibiotic treatment should consider the age of the patient, presence of immunosuppression, and local prevalence of antimicrobial resistance patterns.

• #43 Meningitis – Wikipedia

  https://en.wikipedia.org/wiki/Meningitis

  Administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system’s response to this phenomenon.

• #44

  https://www.who.int/health-topics/meningitis

  The symptoms of meningitis can differ based on the cause, how quickly the disease progresses, how long it lasts, brain involvement, and other serious complications like sepsis. […] Some bacterial pathogens may also account for other symptoms as a result of bloodstream infection, which can quickly lead to sepsis, including cold hands and feet, fast breathing, and low blood pressure. […] Meningitis is a medical emergency and requires urgent medical attention. […] Antibiotic treatment should be started as soon as possible when bacterial meningitis is suspected. […] In non-epidemic settings, intravenous corticosteroids are initiated with the first dose of antibiotics, in order to reduce the inflammatory response and the risk of neurological sequelae and death. […] Vaccines against meningococcal, pneumococcal and Haemophilus influenzae disease have been available for many years. […] No universal vaccine exists. […] Vaccines against GBS are in development. […] Post-exposure prophylaxis with antibiotics is given to close contacts of individuals with meningococcal disease to eradicate asymptomatic meningococcal carriage in the nose and decrease the risk of transmission.

• #45

  https://www.who.int/health-topics/meningitis

  The symptoms of meningitis can differ based on the cause, how quickly the disease progresses, how long it lasts, brain involvement, and other serious complications like sepsis. […] Some bacterial pathogens may also account for other symptoms as a result of bloodstream infection, which can quickly lead to sepsis, including cold hands and feet, fast breathing, and low blood pressure. […] Meningitis is a medical emergency and requires urgent medical attention. […] Antibiotic treatment should be started as soon as possible when bacterial meningitis is suspected. […] In non-epidemic settings, intravenous corticosteroids are initiated with the first dose of antibiotics, in order to reduce the inflammatory response and the risk of neurological sequelae and death. […] Vaccines against meningococcal, pneumococcal and Haemophilus influenzae disease have been available for many years. […] No universal vaccine exists. […] Vaccines against GBS are in development. […] Post-exposure prophylaxis with antibiotics is given to close contacts of individuals with meningococcal disease to eradicate asymptomatic meningococcal carriage in the nose and decrease the risk of transmission.

• #46

  https://www.who.int/news-room/fact-sheets/detail/meningitis

  One in 5 people surviving an episode of bacterial meningitis may have long lasting after-effects. These after-effects include hearing loss, seizures, limb weakness, difficulties with vision, speech, language, memory and communication, as well as scarring and limb amputations after sepsis. […] Antibiotic treatment should be started as soon as possible when bacterial meningitis is suspected. The first dose of antibiotic treatment should not be delayed until the results of the lumbar puncture are available. The choice of antibiotic treatment should consider the age of the patient, presence of immunosuppression, and local prevalence of antimicrobial resistance patterns.

• #47 SciELO Brazil – Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

  https://www.scielo.br/j/anp/a/dMF4mFGHXwjTXSYpR3hnBwp/

  Many brain cells such as astrocytes, glial cells, endothelial cells, ependymal cells, and resident macrophages can produce cytokines and pro-inflammatory molecules in response to bacterial replication and its components. […] The release of large amounts of reactive nitrogen species (RNS) and reactive oxygen species (ROS) had been documented in patient’s populations, likewise, in animal model by pneumococcal meningitis and might contribute to the development of neuronal damage. […] The neuronal damage is caused by the strong inflammatory reaction and direct effects of the microorganism. Significant injury during bacterial meningitis arises from mechanisms of neuronal apoptosis, particularly in the hippocampus; in autopsies cases of bacterial meningitis were found apoptosis of neurons in the dentate gyrus. […] The mortality of S. pneumoniae is (16-37%), N. meningitidis (5%), Haemophilus influenzae (3%). This maintenance of mortality is explained by inflammation in the subarachnoid space caused by the generation of bacterial cell wall components in CSF during treatment of meningitis with antibiotics.

• #48 Pathogenesis and pathophysiology of bacterial meningitis.

  https://pmc.ncbi.nlm.nih.gov/articles/PMC358273/

  Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. […] Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. […] Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

• #49 Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury | Nature Reviews Neuroscience

  https://www.nature.com/articles/nrn1103

  Once bacteria reach the cerebrospinal fluid, their proliferation leads to the increased permeability of the bloodbrain barrier through the release of proinflammatory and toxic compounds, the nature of which has been elucidated in some cases. […] A consequence of the increased permeability and pleocytosis is that neuronal injury takes place in response to increased intracranial pressure, oedema and toxicity. Several molecules have been proposed to elicit cell death, and targeting them constitutes a potential therapeutic strategy against the neurological sequelae that accompany meningitis. […] The elucidation of the molecular pathways that participate in the bacterial infection of the meninges has provided us with new targets to develop preventive and therapeutic strategies. Future studies should continue characterizing these molecular events, and should establish whether other pathogenic bacteria follow similar rules.

• #50 Elucidating the pathogenic mechanism of meningococcal meningitis | Institut Pasteur

  https://www.pasteur.fr/en/elucidating-pathogenic-mechanism-meningococcal-meningitis?language=fr

  If this receptor is absent, N. meningitidis cannot implant in blood vessels and colonize them. […] The researchers have determined that two pilins, PilE and PilV, interact directly with the CD147 receptor. […] Without them, meningococci cannot adhere to endothelial cells. […] These mice were then infected by meningococci naturally having pilins PilE and PilV, or meningococci in which the expression of these pilins had been artificially suppressed. […] The human blood vessels were only infected by meningococci displaying PilE and PilV, which confirms that these two pilins are essential to the bacterial colonization process. […] The researchers also showed in an ex vivo infection model that cerebral vessels and meninges, particularly rich in CD147 receptors, allow colonization by meningococci, unlike other parts of the brain. […] The scientists now wish to develop a new type of vaccine that would block the interaction between N. meningitidis and the CD147 receptors, thereby stopping the bacterium from colonizing the vessels.

• #51 New insights in the mechanisms of bacterial brain invasion during meningitis | Karolinska Institutet

  https://news.ki.se/new-insights-in-the-mechanisms-of-bacterial-brain-invasion-during-meningitis

  The finding that Streptococcus pneumoniae can invade all brain regions is a fundamental piece of knowledge that highlights the need of finding new therapeutic approaches to protect neurons in all brain regions from bacterial interaction, and from PLY exposure. […] PLY, with its incredible capabilities to injure neurons and disrupt neuronal activity, has a major role in the onset of neurological disabilities experienced by up to 70 percent of meningitis survivors. Our goal is to understand bacterial interactions with brain cells to develop new approaches to block such interactions and protect the brain from bacterial infections, says Federico Iovino.

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