Materiały źródłowe

• #1 Hydrocephalus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560875/

  Hydrocephalus is the symptomatic accumulation of cerebrospinal fluid inside the cerebral ventricles. It has complex pathogenesis and different causes. […] Hydrocephalus had complex pathogenesis and multiple causes. […] Normal-pressure hydrocephalus (NPH) is a type of communicating hydrocephalus with increased incidence in older age with a not fully understood pathogenesis. Impaired CSF dynamics cause it with slight or no increase in intracranial pressure (ICP). […] Any physical or functional obstruction within the ventricular system, subarachnoid space, or venous sinuses can be a reason for developing hydrocephalus. An obstructive lesion or gliosis can block CSF flow within the ventricular system. Inflammation or scarring of subarachnoid space or elevated venous pressure within the venous sinuses can impair CSF absorption into the systemic circulation.

• #2 Hydrocephalus in children: Physiology, pathogenesis, and etiology – UpToDate

  https://www.uptodate.com/contents/hydrocephalus-in-children-physiology-pathogenesis-and-etiology/print

  Hydrocephalus is a disorder in which an excessive amount of cerebrospinal fluid (CSF) accumulates within the cerebral ventricles and/or subarachnoid spaces, resulting in ventricular dilation and increased intracranial pressure (ICP). […] The physiology, pathogenesis, and etiology of hydrocephalus will be reviewed here. […] Obstructive hydrocephalus (also called noncommunicating hydrocephalus) refers to excess accumulation of cerebrospinal fluid (CSF) due to structural blockage of CSF flow within the ventricular system. This is the most common form of hydrocephalus in children and is almost always associated with increased intracranial pressure (ICP).

• #3 Hydrocephalus: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1135286-overview

  Hydrocephalus, also known as a hydrodynamic CSF disorder, is broadly defined as a disturbance of cerebrospinal fluid (CSF) formation, flow, or absorption, leading to an increase in volume occupied by this fluid in the central nervous system (CNS). […] Normal CSF production is 0.200.35 mL/min; most CSF is produced by the choroid plexus, which is located within the ventricular system, mainly the lateral and fourth ventricles. The capacity of the lateral and third ventricles in a healthy person is 20 mL. Total volume of CSF in an adult is 120 mL. […] ICP rises if production of CSF exceeds absorption. This occurs if CSF is overproduced, resistance to CSF flow is increased, CSF resorption is decreased, or venous sinus pressure is increased. CSF production falls as ICP rises. Compensation may occur through transventricular absorption (subependymal flow) of CSF and also by absorption along nerve root sleeves (which may result in enlarged optic nerve sheaths). The temporal and frontal horns dilate first, often asymmetrically. This may result in elevation of the corpus callosum, stretching or perforation of the septum pellucidum, thinning of the cerebral mantle, or enlargement of the third ventricle downward into the pituitary fossa (which may cause pituitary dysfunction) as well as dorsal midbrain compression resulting in Parinaud’s syndrome (aralysis of upgaze, Pseudo-Argyll Roberson pupils, convergence-retraction nystagmus, eyelide retraction, and setting sun sign).

• #4 Hydrocephalus – Wikipedia

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

  Hydrocephalus can occur due to birth defects (primary) or can develop later in life (secondary). […] Hydrocephalus can be classified via mechanism into communicating, noncommunicating, ex vacuo, and normal pressure hydrocephalus. […] Hydrocephalus is due to an imbalance between the amount of cerebrospinal fluid (CSF) produced and the amount reabsorbed (or removed from the ventricular system). […] The purpose of cerebrospinal fluid is to provide mechanical support, nutrients, and remove waste from the central nervous system. […] In a person without hydrocephalus, CSF continuously circulates through the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. […] Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.

• #5 Hydrocephalus: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1135286-overview

  Hydrocephalus, also known as a hydrodynamic CSF disorder, is broadly defined as a disturbance of cerebrospinal fluid (CSF) formation, flow, or absorption, leading to an increase in volume occupied by this fluid in the central nervous system (CNS). […] Normal CSF production is 0.200.35 mL/min; most CSF is produced by the choroid plexus, which is located within the ventricular system, mainly the lateral and fourth ventricles. The capacity of the lateral and third ventricles in a healthy person is 20 mL. Total volume of CSF in an adult is 120 mL. […] ICP rises if production of CSF exceeds absorption. This occurs if CSF is overproduced, resistance to CSF flow is increased, CSF resorption is decreased, or venous sinus pressure is increased. CSF production falls as ICP rises. Compensation may occur through transventricular absorption (subependymal flow) of CSF and also by absorption along nerve root sleeves (which may result in enlarged optic nerve sheaths). The temporal and frontal horns dilate first, often asymmetrically. This may result in elevation of the corpus callosum, stretching or perforation of the septum pellucidum, thinning of the cerebral mantle, or enlargement of the third ventricle downward into the pituitary fossa (which may cause pituitary dysfunction) as well as dorsal midbrain compression resulting in Parinaud’s syndrome (aralysis of upgaze, Pseudo-Argyll Roberson pupils, convergence-retraction nystagmus, eyelide retraction, and setting sun sign).

• #6 Hydrocephalus – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hydrocephalus/symptoms-causes/syc-20373604

  Hydrocephalus is caused by an imbalance between how much cerebrospinal fluid is produced and how much is absorbed into the bloodstream. […] Tissues lining the ventricles of the brain produce cerebrospinal fluid. It flows through the ventricles by way of channels. The fluid eventually flows into spaces around the brain and spinal column. It’s absorbed primarily by blood vessels in tissues on the surface of the brain. […] Too much cerebrospinal fluid in the ventricles can occur for one of the following reasons: […] Obstruction. Partial blockage of the flow of cerebrospinal fluid is the most common cause of too much cerebrospinal fluid in the ventricles. A blockage may happen from one ventricle to another or from the ventricles to other spaces around the brain. […] Poor absorption. Less common is a problem with absorbing cerebrospinal fluid. This is often related to inflammation of brain tissues from disease or injury. […] Overproduction. Rarely, cerebrospinal fluid is created more quickly than it can be absorbed.

• #7 Hydrocephalus – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hydrocephalus/symptoms-causes/syc-20373604

  Hydrocephalus is caused by an imbalance between how much cerebrospinal fluid is produced and how much is absorbed into the bloodstream. […] Tissues lining the ventricles of the brain produce cerebrospinal fluid. It flows through the ventricles by way of channels. The fluid eventually flows into spaces around the brain and spinal column. It’s absorbed primarily by blood vessels in tissues on the surface of the brain. […] Too much cerebrospinal fluid in the ventricles can occur for one of the following reasons: […] Obstruction. Partial blockage of the flow of cerebrospinal fluid is the most common cause of too much cerebrospinal fluid in the ventricles. A blockage may happen from one ventricle to another or from the ventricles to other spaces around the brain. […] Poor absorption. Less common is a problem with absorbing cerebrospinal fluid. This is often related to inflammation of brain tissues from disease or injury. […] Overproduction. Rarely, cerebrospinal fluid is created more quickly than it can be absorbed.

• #8 Hydrocephalus – Wikipedia

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

  Hydrocephalus can occur due to birth defects (primary) or can develop later in life (secondary). […] Hydrocephalus can be classified via mechanism into communicating, noncommunicating, ex vacuo, and normal pressure hydrocephalus. […] Hydrocephalus is due to an imbalance between the amount of cerebrospinal fluid (CSF) produced and the amount reabsorbed (or removed from the ventricular system). […] The purpose of cerebrospinal fluid is to provide mechanical support, nutrients, and remove waste from the central nervous system. […] In a person without hydrocephalus, CSF continuously circulates through the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. […] Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.

• #9

  https://link.springer.com/article/10.1007/s11064-024-04113-z

  Temporal changes in CSF dynamics and brain morphometric parameters have been observed in patients with hydrocephalus. […] There are two main categories of the hydrocephalus: obstructive hydrocephalus and communicating hydrocephalus. […] Obstructive hydrocephalus occurs when there is a blockage in the circulation pathway of CSF above the fourth ventricle, preventing it from flowing into the subarachnoid space as it should. […] Common causes of obstructive hydrocephalus include abnormal ventricular structures such as aqueductal stenosis, obstruction of the Monro hole, neural tube malformations, and scar tissue blockage of the CSF circulation pathway caused by tumors, infections, inflammations, and other factors. […] To unravel the causes of CH, it is essential to further explore the mechanisms governing the circulation of CSF. […] Investigating the underlying mechanisms behind these etiologies and exploring the potential development of medications and prenatal nutrients for pregnant women to safeguard against the development of CH in their fetuses would significantly contribute to hydrocephalus prevention efforts.

• #10 Hydrocephalus in children: Physiology, pathogenesis, and etiology – UpToDate

  https://www.uptodate.com/contents/hydrocephalus-in-children-physiology-pathogenesis-and-etiology/print

  Hydrocephalus is a disorder in which an excessive amount of cerebrospinal fluid (CSF) accumulates within the cerebral ventricles and/or subarachnoid spaces, resulting in ventricular dilation and increased intracranial pressure (ICP). […] The physiology, pathogenesis, and etiology of hydrocephalus will be reviewed here. […] Obstructive hydrocephalus (also called noncommunicating hydrocephalus) refers to excess accumulation of cerebrospinal fluid (CSF) due to structural blockage of CSF flow within the ventricular system. This is the most common form of hydrocephalus in children and is almost always associated with increased intracranial pressure (ICP).

• #11 Hydrocephalus | MedLink Neurology

  https://www.medlink.com/articles/hydrocephalus

  There are multiple causes of hydrocephalus. Any condition that alters normal CSF dynamics to cause increased intracranial pressure is a cause of hydrocephalus. Traditionally, they are divided into obstructive and communicating hydrocephalus. Obstructive causes include any lesion that can prevent the normal progress of CSF flow, causing increased pressure proximal to the lesion. The various causes of obstruction include tumors, cysts, congenital aqueductal stenosis, intraventricular hemorrhage, and adhesions resulting from hemorrhage or infection. […] Communicating hydrocephalus is most commonly attributed to inadequate function of the arachnoid granulations for CSF absorption. There is no discrete, identifiable lesion causing the hydrocephalus that can be targeted for treatment. Often, this form occurs in a delayed fashion after some other insult to the brain. It may be seen after any type of intracranial hemorrhage or intracranial surgery and is even occasionally reported after spinal procedures. Infections or other inflammatory conditions may also cause this type of hydrocephalus.

• #12

  https://link.springer.com/article/10.1007/s11064-024-04113-z

  Temporal changes in CSF dynamics and brain morphometric parameters have been observed in patients with hydrocephalus. […] There are two main categories of the hydrocephalus: obstructive hydrocephalus and communicating hydrocephalus. […] Obstructive hydrocephalus occurs when there is a blockage in the circulation pathway of CSF above the fourth ventricle, preventing it from flowing into the subarachnoid space as it should. […] Common causes of obstructive hydrocephalus include abnormal ventricular structures such as aqueductal stenosis, obstruction of the Monro hole, neural tube malformations, and scar tissue blockage of the CSF circulation pathway caused by tumors, infections, inflammations, and other factors. […] To unravel the causes of CH, it is essential to further explore the mechanisms governing the circulation of CSF. […] Investigating the underlying mechanisms behind these etiologies and exploring the potential development of medications and prenatal nutrients for pregnant women to safeguard against the development of CH in their fetuses would significantly contribute to hydrocephalus prevention efforts.

• #13 Hydrocephalus | MedLink Neurology

  https://www.medlink.com/articles/hydrocephalus

  There are multiple causes of hydrocephalus. Any condition that alters normal CSF dynamics to cause increased intracranial pressure is a cause of hydrocephalus. Traditionally, they are divided into obstructive and communicating hydrocephalus. Obstructive causes include any lesion that can prevent the normal progress of CSF flow, causing increased pressure proximal to the lesion. The various causes of obstruction include tumors, cysts, congenital aqueductal stenosis, intraventricular hemorrhage, and adhesions resulting from hemorrhage or infection. […] Communicating hydrocephalus is most commonly attributed to inadequate function of the arachnoid granulations for CSF absorption. There is no discrete, identifiable lesion causing the hydrocephalus that can be targeted for treatment. Often, this form occurs in a delayed fashion after some other insult to the brain. It may be seen after any type of intracranial hemorrhage or intracranial surgery and is even occasionally reported after spinal procedures. Infections or other inflammatory conditions may also cause this type of hydrocephalus.

• #14 Hydrocephalus | MedLink Neurology

  https://www.medlink.com/articles/hydrocephalus

  There are multiple causes of hydrocephalus. Any condition that alters normal CSF dynamics to cause increased intracranial pressure is a cause of hydrocephalus. Traditionally, they are divided into obstructive and communicating hydrocephalus. Obstructive causes include any lesion that can prevent the normal progress of CSF flow, causing increased pressure proximal to the lesion. The various causes of obstruction include tumors, cysts, congenital aqueductal stenosis, intraventricular hemorrhage, and adhesions resulting from hemorrhage or infection. […] Communicating hydrocephalus is most commonly attributed to inadequate function of the arachnoid granulations for CSF absorption. There is no discrete, identifiable lesion causing the hydrocephalus that can be targeted for treatment. Often, this form occurs in a delayed fashion after some other insult to the brain. It may be seen after any type of intracranial hemorrhage or intracranial surgery and is even occasionally reported after spinal procedures. Infections or other inflammatory conditions may also cause this type of hydrocephalus.

• #15 Hydrocephalus | MedLink Neurology

  https://www.medlink.com/articles/hydrocephalus

  There are multiple causes of hydrocephalus. Any condition that alters normal CSF dynamics to cause increased intracranial pressure is a cause of hydrocephalus. Traditionally, they are divided into obstructive and communicating hydrocephalus. Obstructive causes include any lesion that can prevent the normal progress of CSF flow, causing increased pressure proximal to the lesion. The various causes of obstruction include tumors, cysts, congenital aqueductal stenosis, intraventricular hemorrhage, and adhesions resulting from hemorrhage or infection. […] Communicating hydrocephalus is most commonly attributed to inadequate function of the arachnoid granulations for CSF absorption. There is no discrete, identifiable lesion causing the hydrocephalus that can be targeted for treatment. Often, this form occurs in a delayed fashion after some other insult to the brain. It may be seen after any type of intracranial hemorrhage or intracranial surgery and is even occasionally reported after spinal procedures. Infections or other inflammatory conditions may also cause this type of hydrocephalus.

• #16 Hydrocephalus | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/hydrocephalus?lang=us

  Hydrocephalus denotes an increase in the volume of CSF, causing the distension of cerebral ventricles (ventriculomegaly) due to insufficient passage of the CSF from its point of production in the ventricles into the systemic circulation, whether that be via resorption into the dural venous sinuses or via the glymphatic pathway 7. […] Although hydrocephalus is typically referred to as either being „obstructive” or „communicating”, this can lead to confusion as to the underlying cause of ventriculomegaly as the terms are referring to different aspects of the underlying pathophysiology (namely „why” and „where”). […] For example, acute subarachnoid hemorrhage confined to the basal cisterns can result in ventriculomegaly by obstructing the normal flow of CSF through the basal cisterns, and by filling the arachnoid granulations. Even though it is mechanistically an obstruction to CSF flow outside of the ventricular system, it is actually considered as a communicating obstructive hydrocephalus.

• #17 Hydrocephalus | MedLink Neurology

  https://www.medlink.com/articles/hydrocephalus

  There are multiple causes of hydrocephalus. Any condition that alters normal CSF dynamics to cause increased intracranial pressure is a cause of hydrocephalus. Traditionally, they are divided into obstructive and communicating hydrocephalus. Obstructive causes include any lesion that can prevent the normal progress of CSF flow, causing increased pressure proximal to the lesion. The various causes of obstruction include tumors, cysts, congenital aqueductal stenosis, intraventricular hemorrhage, and adhesions resulting from hemorrhage or infection. […] Communicating hydrocephalus is most commonly attributed to inadequate function of the arachnoid granulations for CSF absorption. There is no discrete, identifiable lesion causing the hydrocephalus that can be targeted for treatment. Often, this form occurs in a delayed fashion after some other insult to the brain. It may be seen after any type of intracranial hemorrhage or intracranial surgery and is even occasionally reported after spinal procedures. Infections or other inflammatory conditions may also cause this type of hydrocephalus.

• #18

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  The molecular pathogenesis of hydrocephalus is complex and involves genetic and environmental factors. Ventricular zone disruption is one key pattern in the different forms of the disease. […] This review focuses on the genetics and molecular pathogenesis of human hydrocephalus. We begin by describing the ventricular system and neuroepithelium/ependyma in normal development before reviewing the genetics and molecular biology associated with hydrocephalus. We then describe in detail ventricular/subventricular zone (VZ/SVZ) disruption and dysregulation of cellcell junctions as one critically important common molecular trigger in the pathogenesis of hydrocephalus. […] Disruption of the VZ/SVZ in hydrocephalus is a common event that involves the disassembling, disorganization, or loss of the VZ cells. The VZ/SVZ disruption follows a temporal and spatial program: progression proceeds from caudal to rostral regions, and during neurodevelopment, impairment begins in early fetal stages when the tight junctions disappear.

• #19

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  Additionally, VZ/SVZ disruption seems to follow a common pattern in different hydrocephalic etiologies. Neuroepithelium/ependymal loss has been detected in cases with hydrocephalus associated with SB and communicating hydrocephalus, as well as IVH, demonstrating that disruption is not only present in congenital hydrocephalus but also in acquired hydrocephalus, such as PHH. […] The alterations in cell junctions appear to contribute to the developmental and physiological abnormalities of VZ associated with hydrocephalus, such as the alterations in L1CAM and Aquaporin-4 levels seen in human fetal-onset hydrocephalus. […] In humans, VZ disruption is associated with anomalous ependymal rosettes or heterotopia, abnormalities in neurogenesis that cause SVZ stem cell loss and disruption and AS.

• #20 Hydrocephalus – Wikipedia

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

  Cilia plays a role in the flow of CSF. Cilia are long microtubules on the cell membranes of many cells, including ependymal cells (which line the ventricular system). Some genetic causes of congenital hydrocephalus have been linked to issues with cilia. […] When the cerebrospinal fluid builds up, it causes compression of the brain, which leads to the symptoms of convulsions, intellectual disability, and epileptic seizures. […] CSF can accumulate within the ventricles, this condition is called internal hydrocephalus and may result in increased CSF pressure. […] The production of CSF continues, even when the passages that normally allow it to exit the brain are blocked. Consequently, fluid builds inside the brain, causing pressure that dilates the ventricles and compresses the nervous tissue.

• #21 Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia | Fluids and Barriers of the CNS | Full Text

  https://fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-021-00243-6

  Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. […] There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. […] The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. […] Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface.

• #22 Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia | Fluids and Barriers of the CNS | Full Text

  https://fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-021-00243-6

  Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. […] As the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH. […] The pathophysiology of iNPH has not yet been elucidated, although advanced age and alterations in cerebrospinal fluid (CSF) dynamics have been recognised as potential contributory factors. […] The development of imaging technology has enabled the observation of pulsatile and bidirectional CSF movements that are mainly driven by blood circulation and respiration under normal conditions. […] The coordinated directional beating of ependymal cilia is essential for appropriate CSF flow.

• #23 Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia | Fluids and Barriers of the CNS | Full Text

  https://fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-021-00243-6

  Therefore, motile cilia lining ventricular ependymal surfaces can be considered as a mechanism of ventricular enlargement in the association with CSF stroke volume. […] The impaired beating of ependymal cilia is compounded by decreased apical actin filaments, which leads to motile cilia shedding from the ependymal cells, since the coordinated directional beating of motile cilia contributes to centriole stabilisation. […] It has been demonstrated that the lateral ventricles expand due to the loss or degeneration of ependymal cell coverage on the ventricular surface. […] The cumulative evidence from these studies support the notion of CSF malabsorption as the combined impairment of glymphatic and meningeal lymphatic function is located upstream of ciliary dysfunction in the mechanism of ventricular enlargement in iNPH.

• #24 Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice | Scientific Reports

  https://www.nature.com/articles/s41598-020-69447-4

  Hydrocephalus is a brain disorder triggered by cerebrospinal fluid accumulation in brain cavities. […] Here, we show that deletion of the Rsph9 gene leads to the development of hydrocephalus in the early postnatal period. […] Our results collectively suggested that RSPH9 is essential for ciliary structure and motility of mouse ependymal cilia, and its deletion causes the pathogenesis of hydrocephalus. […] Our study reveals the role of RSPH9 in hydrocephalus pathogenesis and ependymal cilia motility in the developing mouse brain. […] Hydrocephalus was caused by postnatal developmental defects. […] Therefore, deletion of Rsph9 can result in the development of brain dysfunction and progressive hydrocephalus during postnatal development in mice. […] These results show that RSPH9 is necessary for coordinated beating of ependymal cilia. Defects in Rsph9/ ependymal cells can lead to disruption of the pattern of cilia beating and can give rise to hydrocephalus.

• #25 Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice | Scientific Reports

  https://www.nature.com/articles/s41598-020-69447-4

  Hydrocephalus is a brain disorder triggered by cerebrospinal fluid accumulation in brain cavities. […] Here, we show that deletion of the Rsph9 gene leads to the development of hydrocephalus in the early postnatal period. […] Our results collectively suggested that RSPH9 is essential for ciliary structure and motility of mouse ependymal cilia, and its deletion causes the pathogenesis of hydrocephalus. […] Our study reveals the role of RSPH9 in hydrocephalus pathogenesis and ependymal cilia motility in the developing mouse brain. […] Hydrocephalus was caused by postnatal developmental defects. […] Therefore, deletion of Rsph9 can result in the development of brain dysfunction and progressive hydrocephalus during postnatal development in mice. […] These results show that RSPH9 is necessary for coordinated beating of ependymal cilia. Defects in Rsph9/ ependymal cells can lead to disruption of the pattern of cilia beating and can give rise to hydrocephalus.

• #26

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  Additionally, VZ/SVZ disruption seems to follow a common pattern in different hydrocephalic etiologies. Neuroepithelium/ependymal loss has been detected in cases with hydrocephalus associated with SB and communicating hydrocephalus, as well as IVH, demonstrating that disruption is not only present in congenital hydrocephalus but also in acquired hydrocephalus, such as PHH. […] The alterations in cell junctions appear to contribute to the developmental and physiological abnormalities of VZ associated with hydrocephalus, such as the alterations in L1CAM and Aquaporin-4 levels seen in human fetal-onset hydrocephalus. […] In humans, VZ disruption is associated with anomalous ependymal rosettes or heterotopia, abnormalities in neurogenesis that cause SVZ stem cell loss and disruption and AS.

• #27

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  Additionally, VZ/SVZ disruption seems to follow a common pattern in different hydrocephalic etiologies. Neuroepithelium/ependymal loss has been detected in cases with hydrocephalus associated with SB and communicating hydrocephalus, as well as IVH, demonstrating that disruption is not only present in congenital hydrocephalus but also in acquired hydrocephalus, such as PHH. […] The alterations in cell junctions appear to contribute to the developmental and physiological abnormalities of VZ associated with hydrocephalus, such as the alterations in L1CAM and Aquaporin-4 levels seen in human fetal-onset hydrocephalus. […] In humans, VZ disruption is associated with anomalous ependymal rosettes or heterotopia, abnormalities in neurogenesis that cause SVZ stem cell loss and disruption and AS.

• #28

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  It is likely that the denuded ependyma is replaced by reactive astrocytes. […] Inflammation can play an important role in the pathogenesis of hydrocephalus, especially in acquired hydrocephalus such as PHH. The levels of pro-inflammatory molecules, such as interleukins IL-6, tumor necrosis factor-alpha (TNF-alpha), or transforming growth factor-beta (TGF-beta) in the CSF correlate with the severity of hydrocephalus. […] Molecular biological studies are urgently needed to rigorously investigate these novel pathways, including those involved in inflammation, VZ disruption, alterations in cellcell junctions, and aberrant precursor cell biology.

• #29 Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice | Scientific Reports

  https://www.nature.com/articles/s41598-020-69447-4

  Hydrocephalus in Rsph9/ mice results in astrogliosis, microgliosis and cerebrovascular abnormalities. […] The hydrocephalus caused by Rsph9 deletion was accompanied by astrogliosis and microgliosis in the cortex. […] Hydrocephalus proceeds with reactive astrogliosis and microgliosis, which lead to the formation of glial scars.

• #30

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  It is likely that the denuded ependyma is replaced by reactive astrocytes. […] Inflammation can play an important role in the pathogenesis of hydrocephalus, especially in acquired hydrocephalus such as PHH. The levels of pro-inflammatory molecules, such as interleukins IL-6, tumor necrosis factor-alpha (TNF-alpha), or transforming growth factor-beta (TGF-beta) in the CSF correlate with the severity of hydrocephalus. […] Molecular biological studies are urgently needed to rigorously investigate these novel pathways, including those involved in inflammation, VZ disruption, alterations in cellcell junctions, and aberrant precursor cell biology.

• #31 Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets | Nature Reviews Neurology

  https://www.nature.com/articles/s41582-020-0321-y

  Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. […] Recent data have begun to uncover the molecular mechanisms by which inflammation driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways contributes to the pathogenesis of hydrocephalus. […] We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glialymphatic) CSF pathways. […] Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention.

• #32 Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets | Nature Reviews Neurology

  https://www.nature.com/articles/s41582-020-0321-y

  Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. […] Recent data have begun to uncover the molecular mechanisms by which inflammation driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways contributes to the pathogenesis of hydrocephalus. […] We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glialymphatic) CSF pathways. […] Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention.

• #33 Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets | Nature Reviews Neurology

  https://www.nature.com/articles/s41582-020-0321-y

  Posthaemorrhagic hydrocephalus and postinfectious hydrocephalus are the most common causes of hydrocephalus and are both characterized by inflammation in the brain tissue and CSF space. […] Recent data have begun to uncover the molecular mechanisms by which inflammation, driven by activation of Toll-like receptor 4, contributes to the pathogenesis of hydrocephalus. […] Pharmacotherapeutic approaches that target inflammation have the potential to address multiple drivers of posthaemorrhagic hydrocephalus and postinfectious hydrocephalus, including acute hypersecretion of CSF by the choroid plexus epithelium and scarring of CSF drainage pathways.

• #34 Molecular mechanism of hydrocephalus could lead to the first-ever non-surgical treatment | ScienceDaily

  https://www.sciencedaily.com/releases/2023/03/230308112221.htm

  Mass General researchers have discovered a novel molecular mechanism responsible for the most common forms of acquired hydrocephalus, potentially opening the door to the first-ever nonsurgical treatment for a life-threatening disease that affects about a million Americans. […] The team uncovered in animal models the pathway through which infection or bleeding in the brain triggers a massive neuroinflammatory response that results in increased production of cerebrospinal fluid (CSF) by tissue known as the choroid plexus, leading to swelling of the brain ventricles. […] We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. […] By deciphering the unique cellular and molecular biology that occurs within the brain after infection or severe hemorrhage, the MGH-led research team has taken a major step toward nonsurgical, pharmacologic treatment for humans.

• #35 New Insights by Mass General on the molecular mechanism of hydrocephalus could lead to the first-ever non-surgical treatment

  https://www.massgeneral.org/news/press-release/new-insights-by-mass-general-on-the-molecular-mechanism-of-hydrocephalus%20could-lead-to-the-first-ever-non-surgical-treatment

  Researchers have learned that the same molecular pathway is involved in both the infectious and hemorrhagic forms of acquired hydrocephalus, a life-threatening disease that triggers a massive neuroinflammatory response and swelling of the ventricles of the brain. […] As reported in the journal Cell, the team uncovered in animal models the pathway through which infection or bleeding in the brain triggers a massive neuroinflammatory response that results in increased production of cerebrospinal fluid (CSF) by tissue known as the choroid plexus, leading to swelling of the brain ventricles. […] Weve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. […] By deciphering the unique cellular and molecular biology that occurs within the brain after infection or severe hemorrhage, the MGH-led research team has taken a major step toward nonsurgical, pharmacologic treatment for humans.

• #36 Molecular mechanism of hydrocephalus could lead to the first-ever non-surgical treatment | ScienceDaily

  https://www.sciencedaily.com/releases/2023/03/230308112221.htm

  An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain — a so-called „cytokine storm,” or immune system overreaction, so often seen in COVID-19 infections — swelling the brain ventricles. […] Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.

• #37 New Insights by Mass General on the molecular mechanism of hydrocephalus could lead to the first-ever non-surgical treatment

  https://www.massgeneral.org/news/press-release/new-insights-by-mass-general-on-the-molecular-mechanism-of-hydrocephalus%20could-lead-to-the-first-ever-non-surgical-treatment

  An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain a so-called cytokine storm, or immune system overreaction, so often seen in COVID-19 infections–swelling the brain ventricles. […] Dr. Kahles lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug thats been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.

• #38 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20230308/Novel-molecular-mechanism-responsible-for-common-form-of-acquired-hydrocephalus-discovered.aspx

  An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain a so-called „cytokine storm,” or immune system overreaction, so often seen in COVID-19 infections–swelling the brain ventricles. […] Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection. […] MGH researchers are continuing to explore how rapamycin and other repurposed drugs which quell the inflammation seen in acquired hydrocephalus could be turned into an effective drug treatment for patients.

• #39 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20230308/Novel-molecular-mechanism-responsible-for-common-form-of-acquired-hydrocephalus-discovered.aspx

  An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain a so-called „cytokine storm,” or immune system overreaction, so often seen in COVID-19 infections–swelling the brain ventricles. […] Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection. […] MGH researchers are continuing to explore how rapamycin and other repurposed drugs which quell the inflammation seen in acquired hydrocephalus could be turned into an effective drug treatment for patients.

• #40 Review of theories into the pathogenesis of normal pressure hydrocephalus | BMJ Neurology Open

  https://neurologyopen.bmj.com/content/6/2/e000804

  Normal pressure hydrocephalus (NPH) represents a unique form of hydrocephalus characterised by the paradox of ventriculomegaly without significant elevations in intracranial pressure, with the clinical triad of gait instability, cognitive impairment, and urinary incontinence. […] A myriad of neurobiological correlates have been implicated in its pathophysiology. […] NPH represents a unique form of hydrocephalus manifesting as a disorder of the cerebral vasculature, characterised by arteriosclerosis and reduced intracranial elastance. There are multiple mechanisms underlying its pathophysiology, which include windkessel impairment causing redistribution of intracranial pulsatility from the subarachnoid space to the ventricles, reductions in cerebral blood flow, impaired glymphatic clearance, reduced bloodbrain barrier integrity and alterations in venous haemodynamics.

• #41 Normal pressure hydrocephalus – Wikipedia

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

  Normal pressure hydrocephalus (NPH), also called malresorptive hydrocephalus, is a form of communicating hydrocephalus in which excess cerebrospinal fluid (CSF) builds up in the ventricles, leading to normal or slightly elevated cerebrospinal fluid pressure. […] Although the cause of idiopathic (also referred to as primary) NPH remains unclear, it has been associated with various co-morbidities including hypertension, diabetes mellitus, Alzheimer’s disease, and hyperlipidemia. […] Causes of secondary NPH include trauma, hemorrhage, or infection. […] The exact pathogenesis is unknown, but consensus on some mechanisms include: An imbalance exists between production and resorption of CSF. The resistance to CSF outflow is often elevated. The disease is not caused by overproduction of CSF or obstruction of CSF flow at the ventricles.

• #42 Normal pressure hydrocephalus – Wikipedia

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

  Normal pressure hydrocephalus (NPH), also called malresorptive hydrocephalus, is a form of communicating hydrocephalus in which excess cerebrospinal fluid (CSF) builds up in the ventricles, leading to normal or slightly elevated cerebrospinal fluid pressure. […] Although the cause of idiopathic (also referred to as primary) NPH remains unclear, it has been associated with various co-morbidities including hypertension, diabetes mellitus, Alzheimer’s disease, and hyperlipidemia. […] Causes of secondary NPH include trauma, hemorrhage, or infection. […] The exact pathogenesis is unknown, but consensus on some mechanisms include: An imbalance exists between production and resorption of CSF. The resistance to CSF outflow is often elevated. The disease is not caused by overproduction of CSF or obstruction of CSF flow at the ventricles.

• #43 Review of theories into the pathogenesis of normal pressure hydrocephalus | BMJ Neurology Open

  https://neurologyopen.bmj.com/content/6/2/e000804

  The underlying pathophysiology of NPH has been of great interest over the years, with various theories presented to account for the underpinnings of its peculiar clinical presentation. […] While various theories have been proposed since Adams et als findings to account for the symptomatology and pathophysiology of NPH, a definitive theory of pathogenesis is still lacking. […] There are a myriad of biological processes implicated in NPH, ranging from arteriosclerosis, and impaired blood flow, to impairments in the glymphatic pathway, to disturbances in the distribution of intracranial pulsatility. […] Recent theories have pointed towards this condition being a disorder of intracranial vasculature. […] Moreover, there is substantive literature analysing forms of hydrocephalus as disorders of intracranial pulsatility.

• #44 Review of theories into the pathogenesis of normal pressure hydrocephalus | BMJ Neurology Open

  https://neurologyopen.bmj.com/content/6/2/e000804

  Impairments in the glymphatic system have also been implicated in NPH. […] This impairment in glymphatic flow has been implicated in experimentally observed retrograde aqueductal flow in NPH patients, which reverts to anterograde flow following CSF diversion via shunting. […] Therefore, BBB dysfunction may also provide, in part, a mechanism through which the various pathological processes outlined above may contribute to NPH. […] NPH can, therefore, be seen as a clinical manifestation of multiple pathophysiological processes, ranging from impairments in CBF, to impaired vascular and arterial compliance, to cerebral windkessel impairment causing pathological redistribution of intracranial pulsatility, to impairments of glymphatic flow and BBB function.

• #45 Review of theories into the pathogenesis of normal pressure hydrocephalus | BMJ Neurology Open

  https://neurologyopen.bmj.com/content/6/2/e000804

  Impairments in the glymphatic system have also been implicated in NPH. […] This impairment in glymphatic flow has been implicated in experimentally observed retrograde aqueductal flow in NPH patients, which reverts to anterograde flow following CSF diversion via shunting. […] Therefore, BBB dysfunction may also provide, in part, a mechanism through which the various pathological processes outlined above may contribute to NPH. […] NPH can, therefore, be seen as a clinical manifestation of multiple pathophysiological processes, ranging from impairments in CBF, to impaired vascular and arterial compliance, to cerebral windkessel impairment causing pathological redistribution of intracranial pulsatility, to impairments of glymphatic flow and BBB function.

• #46 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. […] The pathophysiology of hydrocephalus is unclear. […] However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. […] Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. […] We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. […] Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation.

• #47 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162

  Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. […] The pathophysiology of hydrocephalus is unclear. […] However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. […] Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. […] We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. […] Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation. […] Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. […] There is substantial evidence to support this theory, and further studies may help solidify the merit of this hypothesis.

• #48 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. […] The pathophysiology of hydrocephalus is unclear. […] However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. […] Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. […] We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. […] Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation.

• #49 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162

  Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. […] The pathophysiology of hydrocephalus is unclear. […] However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. […] Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. […] We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. […] Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation. […] Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. […] There is substantial evidence to support this theory, and further studies may help solidify the merit of this hypothesis.

• #50 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. […] The importance of the role played by excess macromolecules in the ventricles in hydrocephalus is strengthened by the relief of hydrocephalus in situations that decrease the amount of macromolecules in the CSF. […] The elimination of macromolecules results in the relief of hydrocephalus, which may be explained by the decrease in the osmotic load and the reduction of the macromolecules biological effect on the brain and CSF secretion. […] These results suggest that water transport into the ventricles is secondary to the osmotic load or the amount of macromolecules in the ventricles. […] Hydrocephalus is a complex condition resulting from a wide variety of different disorders.

• #51 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. […] The importance of the role played by excess macromolecules in the ventricles in hydrocephalus is strengthened by the relief of hydrocephalus in situations that decrease the amount of macromolecules in the CSF. […] The elimination of macromolecules results in the relief of hydrocephalus, which may be explained by the decrease in the osmotic load and the reduction of the macromolecules biological effect on the brain and CSF secretion. […] These results suggest that water transport into the ventricles is secondary to the osmotic load or the amount of macromolecules in the ventricles. […] Hydrocephalus is a complex condition resulting from a wide variety of different disorders.

• #52 The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

  https://www.mdpi.com/1422-0067/22/9/5050

  Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH) and reportedly contributes to poor neurological outcomes. […] Various mechanisms have been implicated for the development of chronic hydrocephalus following aSAH, including alterations in cerebral spinal fluid (CSF) dynamics, obstruction of the arachnoid granulations by blood products, and adhesions within the ventricular system. […] Regarding molecular mechanisms that cause chronic hydrocephalus following aSAH, we carried out an extensive review of animal studies and clinical trials about the transforming growth factor-β/SMAD signaling pathway, upregulation of tenascin-C, inflammation-dependent hypersecretion of CSF, systemic inflammatory response syndrome, and immune dysregulation. […] Following aSAH, evidence suggests that extensive fibrosis in the subarachnoid space may be an important cause of chronic hydrocephalus development.

• #53 The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

  https://www.mdpi.com/1422-0067/22/9/5050

  Post-hemorrhagic blood-clotting products with fibrosis of the leptomeninges and arachnoid granulations may reduce the circulation of CSF, suppress CSF absorption, and reduce drainage, leading to the development of hydrocephalus. […] TGF-β1 levels have been reported to be higher in the CSF following aSAH, especially in patients with hydrocephalus, which implies its role in the pathogenesis of subarachnoid fibrosis and chronic hydrocephalus following aSAH. […] The expression of tenascin-C (TNC), a matricellular protein, is extremely low in adult tissues under normal physiological conditions. […] TNC may cause leptomeningeal collagen synthesis and fibrosis, as well as brain injuries with decreased brain parenchymal volume contributing to subsequent ventricular enlargement, resulting in the development of chronic hydrocephalus.

• #54 The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

  https://www.mdpi.com/1422-0067/22/9/5050

  Post-hemorrhagic blood-clotting products with fibrosis of the leptomeninges and arachnoid granulations may reduce the circulation of CSF, suppress CSF absorption, and reduce drainage, leading to the development of hydrocephalus. […] TGF-β1 levels have been reported to be higher in the CSF following aSAH, especially in patients with hydrocephalus, which implies its role in the pathogenesis of subarachnoid fibrosis and chronic hydrocephalus following aSAH. […] The expression of tenascin-C (TNC), a matricellular protein, is extremely low in adult tissues under normal physiological conditions. […] TNC may cause leptomeningeal collagen synthesis and fibrosis, as well as brain injuries with decreased brain parenchymal volume contributing to subsequent ventricular enlargement, resulting in the development of chronic hydrocephalus.

• #55 The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

  https://www.mdpi.com/1422-0067/22/9/5050

  Post-hemorrhagic blood-clotting products with fibrosis of the leptomeninges and arachnoid granulations may reduce the circulation of CSF, suppress CSF absorption, and reduce drainage, leading to the development of hydrocephalus. […] TGF-β1 levels have been reported to be higher in the CSF following aSAH, especially in patients with hydrocephalus, which implies its role in the pathogenesis of subarachnoid fibrosis and chronic hydrocephalus following aSAH. […] The expression of tenascin-C (TNC), a matricellular protein, is extremely low in adult tissues under normal physiological conditions. […] TNC may cause leptomeningeal collagen synthesis and fibrosis, as well as brain injuries with decreased brain parenchymal volume contributing to subsequent ventricular enlargement, resulting in the development of chronic hydrocephalus.

• #56 Mechanisms of hydrocephalus after intraventricular haemorrhage in adults | Stroke and Vascular Neurology

  https://svn.bmj.com/content/1/1/23

  Intraventricular haemorrhage (IVH) is defined as the eruption of blood in the cerebroventricular system and occurs mostly secondary to intracerebral haemorrhage (ICH) in adults. Hydrocephalus is a severe complication of IVH that can serve as an independent predictor of increased mortality. […] We focus on the mechanisms of hydrocephalus after adult IVH, including blood-clot blockage, barrier impairment, inflammation and blood components, and attempt to reconcile the current research findings into a unified framework. […] Both immediate and delayed hydrocephalus are possible following IVH, yet the mechanisms by which they occur are unclear. […] Mechanistic understanding of the events that lead to IVH and subsequent hydrocephalus will guide both clinical research and basic-science experiments geared towards treating these conditions.

• #57 Mechanisms of hydrocephalus after intraventricular haemorrhage in adults | Stroke and Vascular Neurology

  https://svn.bmj.com/content/1/1/23

  Currently, the prevailing theory explaining acute IVH-induced hydrocephalus is blood-clot blockage in the CSF drainage pathway. […] After IVH, obstructive hydrocephalus can occur immediately. […] Advances in our understanding of the mechanism of hydrocephalus following IVH have been aided by observations in experimental animals. […] The total blood volume and duration of blood and blood-clot presence in the ventricular system are the main factors contributing to the intensity of communicating hydrocephalus, which occurs mostly in a delayed phase when an inflammatory reaction is generated as a result of the debris accumulating as the blood products are broken down. […] Hydrocephalus occurs because of increased production, inappropriate flow or decreased reabsorption of CSF. […] Two complementary mechanisms underlying ependymal cell damage and leading to hydrocephalus following IVH have been proposed: (1) disruption of the ependymal surface (cells and their cilia) results in collapse of the cerebral aqueduct walls or in aqueductal stenosis and CSF flow occlusion and (2) IVH leads to failure regulating the transfer of fluid, ions and small molecules between the cerebral parenchyma and the ventricular fluid, due to injury-caused dysfunction of the ependymal cells.

• #58 Mechanisms of hydrocephalus after intraventricular haemorrhage in adults | Stroke and Vascular Neurology

  https://svn.bmj.com/content/1/1/23

  Currently, the prevailing theory explaining acute IVH-induced hydrocephalus is blood-clot blockage in the CSF drainage pathway. […] After IVH, obstructive hydrocephalus can occur immediately. […] Advances in our understanding of the mechanism of hydrocephalus following IVH have been aided by observations in experimental animals. […] The total blood volume and duration of blood and blood-clot presence in the ventricular system are the main factors contributing to the intensity of communicating hydrocephalus, which occurs mostly in a delayed phase when an inflammatory reaction is generated as a result of the debris accumulating as the blood products are broken down. […] Hydrocephalus occurs because of increased production, inappropriate flow or decreased reabsorption of CSF. […] Two complementary mechanisms underlying ependymal cell damage and leading to hydrocephalus following IVH have been proposed: (1) disruption of the ependymal surface (cells and their cilia) results in collapse of the cerebral aqueduct walls or in aqueductal stenosis and CSF flow occlusion and (2) IVH leads to failure regulating the transfer of fluid, ions and small molecules between the cerebral parenchyma and the ventricular fluid, due to injury-caused dysfunction of the ependymal cells.

• #59 Mechanisms of hydrocephalus after intraventricular haemorrhage in adults | Stroke and Vascular Neurology

  https://svn.bmj.com/content/1/1/23

  Currently, the prevailing theory explaining acute IVH-induced hydrocephalus is blood-clot blockage in the CSF drainage pathway. […] After IVH, obstructive hydrocephalus can occur immediately. […] Advances in our understanding of the mechanism of hydrocephalus following IVH have been aided by observations in experimental animals. […] The total blood volume and duration of blood and blood-clot presence in the ventricular system are the main factors contributing to the intensity of communicating hydrocephalus, which occurs mostly in a delayed phase when an inflammatory reaction is generated as a result of the debris accumulating as the blood products are broken down. […] Hydrocephalus occurs because of increased production, inappropriate flow or decreased reabsorption of CSF. […] Two complementary mechanisms underlying ependymal cell damage and leading to hydrocephalus following IVH have been proposed: (1) disruption of the ependymal surface (cells and their cilia) results in collapse of the cerebral aqueduct walls or in aqueductal stenosis and CSF flow occlusion and (2) IVH leads to failure regulating the transfer of fluid, ions and small molecules between the cerebral parenchyma and the ventricular fluid, due to injury-caused dysfunction of the ependymal cells.

• #60 Hydrocephalus Associated with Myelomeningocele | IntechOpen

  https://www.intechopen.com/chapters/86588

  Hydrocephalus (HCP) is one of the most common associations of myelomeningocele, and it may be overt and present at birth or be latent and develop following the repair of myelomeningocele. […] Several obstructive and absorptive factors act together to cause hydrocephalus in patients with myelomeningocele. […] The unified theory proposed by McLone and Knepper is the most popular postulation for the evolution of hydrocephalus in patients with myelomeningocele. It postulates that persistent CSF loss from the neural tube defect impairs brain and CSF pathways development, which results in the downward displacement of the brain stem and crowding of the posterior fossa that leads to hydrocephalus. […] Type II Chiari malformation with an overcrowded posterior fossa causes obstruction of the fourth ventricular outlets and disturbance in the flow of cerebrospinal fluid at the craniocervical junction, and it is the major factor responsible for obstructive hydrocephalus in patients with myelomeningocele.

• #61 Hydrocephalus Associated with Myelomeningocele | IntechOpen

  https://www.intechopen.com/chapters/86588

  Hydrocephalus (HCP) is one of the most common associations of myelomeningocele, and it may be overt and present at birth or be latent and develop following the repair of myelomeningocele. […] Several obstructive and absorptive factors act together to cause hydrocephalus in patients with myelomeningocele. […] The unified theory proposed by McLone and Knepper is the most popular postulation for the evolution of hydrocephalus in patients with myelomeningocele. It postulates that persistent CSF loss from the neural tube defect impairs brain and CSF pathways development, which results in the downward displacement of the brain stem and crowding of the posterior fossa that leads to hydrocephalus. […] Type II Chiari malformation with an overcrowded posterior fossa causes obstruction of the fourth ventricular outlets and disturbance in the flow of cerebrospinal fluid at the craniocervical junction, and it is the major factor responsible for obstructive hydrocephalus in patients with myelomeningocele.

• #62 Hydrocephalus Associated with Myelomeningocele | IntechOpen

  https://www.intechopen.com/chapters/86588

  Hydrocephalus (HCP) is one of the most common associations of myelomeningocele, and it may be overt and present at birth or be latent and develop following the repair of myelomeningocele. […] Several obstructive and absorptive factors act together to cause hydrocephalus in patients with myelomeningocele. […] The unified theory proposed by McLone and Knepper is the most popular postulation for the evolution of hydrocephalus in patients with myelomeningocele. It postulates that persistent CSF loss from the neural tube defect impairs brain and CSF pathways development, which results in the downward displacement of the brain stem and crowding of the posterior fossa that leads to hydrocephalus. […] Type II Chiari malformation with an overcrowded posterior fossa causes obstruction of the fourth ventricular outlets and disturbance in the flow of cerebrospinal fluid at the craniocervical junction, and it is the major factor responsible for obstructive hydrocephalus in patients with myelomeningocele.

• #63 Hydrocephalus Associated with Myelomeningocele | IntechOpen

  https://www.intechopen.com/chapters/86588

  There may be associated stenosis or forking of the cerebral aqueduct, also causing obstruction to CSF flow. […] The crowded posterior fossa results in venous compression, which leads to increased venous pressure that impedes CSF absorption. […] Furthermore, there is a higher resistance to the flow of CSF across the tentorial hiatus and there may be associated underdevelopment of the arachnoid granulations, which results in impaired or inadequate CSF absorption. […] These factors result in progressive ventriculomegaly and raised intracranial pressure if unchecked, which are responsible for the clinical and radiologic features of hydrocephalus seen in these patients.

• #64 Hydrocephalus Associated with Myelomeningocele | IntechOpen

  https://www.intechopen.com/chapters/86588

  There may be associated stenosis or forking of the cerebral aqueduct, also causing obstruction to CSF flow. […] The crowded posterior fossa results in venous compression, which leads to increased venous pressure that impedes CSF absorption. […] Furthermore, there is a higher resistance to the flow of CSF across the tentorial hiatus and there may be associated underdevelopment of the arachnoid granulations, which results in impaired or inadequate CSF absorption. […] These factors result in progressive ventriculomegaly and raised intracranial pressure if unchecked, which are responsible for the clinical and radiologic features of hydrocephalus seen in these patients.

• #65 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. […] The importance of the role played by excess macromolecules in the ventricles in hydrocephalus is strengthened by the relief of hydrocephalus in situations that decrease the amount of macromolecules in the CSF. […] The elimination of macromolecules results in the relief of hydrocephalus, which may be explained by the decrease in the osmotic load and the reduction of the macromolecules biological effect on the brain and CSF secretion. […] These results suggest that water transport into the ventricles is secondary to the osmotic load or the amount of macromolecules in the ventricles. […] Hydrocephalus is a complex condition resulting from a wide variety of different disorders.

• #66 Hydrocephalus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560875/

  Hydrocephalus is the symptomatic accumulation of cerebrospinal fluid inside the cerebral ventricles. It has complex pathogenesis and different causes. […] Hydrocephalus had complex pathogenesis and multiple causes. […] Normal-pressure hydrocephalus (NPH) is a type of communicating hydrocephalus with increased incidence in older age with a not fully understood pathogenesis. Impaired CSF dynamics cause it with slight or no increase in intracranial pressure (ICP). […] Any physical or functional obstruction within the ventricular system, subarachnoid space, or venous sinuses can be a reason for developing hydrocephalus. An obstructive lesion or gliosis can block CSF flow within the ventricular system. Inflammation or scarring of subarachnoid space or elevated venous pressure within the venous sinuses can impair CSF absorption into the systemic circulation.

• #67 Hydrocephalus – Wikipedia

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

  Hydrocephalus can occur due to birth defects (primary) or can develop later in life (secondary). […] Hydrocephalus can be classified via mechanism into communicating, noncommunicating, ex vacuo, and normal pressure hydrocephalus. […] Hydrocephalus is due to an imbalance between the amount of cerebrospinal fluid (CSF) produced and the amount reabsorbed (or removed from the ventricular system). […] The purpose of cerebrospinal fluid is to provide mechanical support, nutrients, and remove waste from the central nervous system. […] In a person without hydrocephalus, CSF continuously circulates through the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. […] Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.

• #68

  https://journals.lww.com/neur/fulltext/2021/69002/genetics_and_molecular_pathogenesis_of_human.4.aspx

  The molecular pathogenesis of hydrocephalus is complex and involves genetic and environmental factors. Ventricular zone disruption is one key pattern in the different forms of the disease. […] This review focuses on the genetics and molecular pathogenesis of human hydrocephalus. We begin by describing the ventricular system and neuroepithelium/ependyma in normal development before reviewing the genetics and molecular biology associated with hydrocephalus. We then describe in detail ventricular/subventricular zone (VZ/SVZ) disruption and dysregulation of cellcell junctions as one critically important common molecular trigger in the pathogenesis of hydrocephalus. […] Disruption of the VZ/SVZ in hydrocephalus is a common event that involves the disassembling, disorganization, or loss of the VZ cells. The VZ/SVZ disruption follows a temporal and spatial program: progression proceeds from caudal to rostral regions, and during neurodevelopment, impairment begins in early fetal stages when the tight junctions disappear.

• #69 Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets | Nature Reviews Neurology

  https://www.nature.com/articles/s41582-020-0321-y

  Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. […] Recent data have begun to uncover the molecular mechanisms by which inflammation driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways contributes to the pathogenesis of hydrocephalus. […] We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glialymphatic) CSF pathways. […] Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention.

• #70 New concepts in the pathogenesis of hydrocephalus – Krishnamurthy – Translational Pediatrics

  https://tp.amegroups.org/article/view/4162/html

  Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. […] The pathophysiology of hydrocephalus is unclear. […] However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. […] Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. […] We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. […] Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation.

• #71 Review of theories into the pathogenesis of normal pressure hydrocephalus | BMJ Neurology Open

  https://neurologyopen.bmj.com/content/6/2/e000804

  The underlying pathophysiology of NPH has been of great interest over the years, with various theories presented to account for the underpinnings of its peculiar clinical presentation. […] While various theories have been proposed since Adams et als findings to account for the symptomatology and pathophysiology of NPH, a definitive theory of pathogenesis is still lacking. […] There are a myriad of biological processes implicated in NPH, ranging from arteriosclerosis, and impaired blood flow, to impairments in the glymphatic pathway, to disturbances in the distribution of intracranial pulsatility. […] Recent theories have pointed towards this condition being a disorder of intracranial vasculature. […] Moreover, there is substantive literature analysing forms of hydrocephalus as disorders of intracranial pulsatility.

• #72 Molecular mechanism of hydrocephalus could lead to the first-ever non-surgical treatment | ScienceDaily

  https://www.sciencedaily.com/releases/2023/03/230308112221.htm

  Mass General researchers have discovered a novel molecular mechanism responsible for the most common forms of acquired hydrocephalus, potentially opening the door to the first-ever nonsurgical treatment for a life-threatening disease that affects about a million Americans. […] The team uncovered in animal models the pathway through which infection or bleeding in the brain triggers a massive neuroinflammatory response that results in increased production of cerebrospinal fluid (CSF) by tissue known as the choroid plexus, leading to swelling of the brain ventricles. […] We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. […] By deciphering the unique cellular and molecular biology that occurs within the brain after infection or severe hemorrhage, the MGH-led research team has taken a major step toward nonsurgical, pharmacologic treatment for humans.

• #73 Researchers Identify Crucial Link Between Immune System and Development of Acquired Hydrocephalus < Yale School of Medicine

  https://medicine.yale.edu/news-article/researchers-identify-crucial-link-between-the-immune-system-and-the-development-of-acquired-hydrocephalus/

  Researchers in the Department of Neurosurgery at Yale School of Medicine have discovered the immune-mediated pathobiological process underlying two common types of acquired hydrocephalus. […] They identified that intraventricular infection and hemorrhage trigger a strikingly similar immune response within the choroid plexus. Furthermore, they found that this immune-mediated reaction catalyzes the choroid plexus to produce more CSF than usual, ultimately leading to fluid accumulation and hydrocephalus. […] „It demonstrates that post-hemorrhagic and post-infectious hydrocephalus have a common underlying pathophysiology mediated by the choroid plexus, and it identifies the peripheral immune response as an important key component of this pathobiological response.” […] Not only does this work uncover a similar and novel inflammatory mechanism driving these two common forms of acquired hydrocephalus, but it also demonstrates that by targeting the peripheral immune system with systemic immunomodulation, we are able to modulate the choroid plexus response and decrease CSF hypersecretion leading to hydrocephalus.

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