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The Journal of Experimental Medicine Aug 2022A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et...
A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220035) employ light sheet fluorescence imaging of intact mouse heads to provide a more comprehensive chart of the meningeal lymphatic vasculature and draw a parallel between lymphatic drainage of cerebrospinal fluid in mice and humans.
Topics: Animals; Brain; Lymphatic System; Lymphatic Vessels; Mammals; Meninges; Mice; Spinal Cord
PubMed: 35789368
DOI: 10.1084/jem.20220891 -
Science Immunology Oct 2023High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CNS) from infection being...
High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CNS) from infection being immature and not fully developed. However, the mechanisms by which pathogens breach CNS barriers are poorly understood. Using the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) to study virus propagation into the CNS during systemic infection, we demonstrate that mortality in neonatal, but not adult, mice is high after infection. Virus propagated extensively from the perivenous sinus region of the dura mater to the leptomeninges, choroid plexus, and cerebral cortex. Although the structural barrier of CNS border tissues is comparable between neonates and adults, immunofluorescence staining and single-cell RNA sequencing analyses revealed that the neonatal dural immune cells are immature and predominantly composed of CD206 macrophages, with major histocompatibility complex class II (MHCII) macrophages being rare. In adults, however, perivenous sinus immune cells were enriched in MHCII macrophages that are specialized for producing antiviral molecules and chemokines compared with CD206 macrophages and protected the CNS against systemic virus invasion. Our findings clarify how systemic pathogens enter the CNS through its border tissues and how the immune barrier at the perivenous sinus region of the dura blocks pathogen access to the CNS.
Topics: Mice; Animals; Central Nervous System; Meningoencephalitis; Lymphocytic Choriomeningitis; Meninges; Lymphocytic choriomeningitis virus; Meningitis, Viral; Encephalitis, Viral
PubMed: 37801517
DOI: 10.1126/sciimmunol.adg6155 -
Topics in Magnetic Resonance Imaging :... Apr 2017Leptomeningeal collaterals provide the primary source of perfusion to ischemic brain tissue following the onset of acute ischemic stroke and are becoming an important... (Review)
Review
Leptomeningeal collaterals provide the primary source of perfusion to ischemic brain tissue following the onset of acute ischemic stroke and are becoming an important imaging biomarker for stroke therapy triage. Collateral circulation is predictive of infarct growth, end infarct volume, and response to endovascular therapy. The strength of the collateral circulation varies among patients and is partially dependent on genetic and modifiable risk factors. Collateral circulation may be assessed by standard angiographic techniques, including digital subtraction angiography, computed tomography and magnetic resonance (MR) angiography, as well as a growing array of advanced MR techniques including arterial spin labeling and dynamic MR angiography. Simple scoring systems are used to estimate the relative strength of the collateral circulation for a given patient, although there are some discrepancies in the predictive value of these systems. In this review, we discuss methods and techniques for determining the robustness of the collateral circulation and the role of the collateral circulation in acute ischemic stroke assessment and triage.
Topics: Animals; Brain; Cerebrovascular Circulation; Collateral Circulation; Humans; Meninges; Neuroimaging; Stroke
PubMed: 28277461
DOI: 10.1097/RMR.0000000000000123 -
Neuroscience Dec 2016Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic... (Review)
Review
Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine are still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. However, the role of vasodilation in migraine is unclear and recent findings challenge its necessity. While vasodilation itself may not contribute to migraine, it remains possible that vessels play a role in migraine pathophysiology in the absence of vasodilation. Blood vessels consist of a variety of cell types that both release and respond to numerous mediators including growth factors, cytokines, adenosine triphosphate (ATP), and nitric oxide (NO). Many of these mediators have actions on neurons that can contribute to migraine. Conversely, neurons release factors such as norepinephrine and calcitonin gene-related peptide (CGRP) that act on cells native to blood vessels. Both normal and pathological events occurring within and between vascular cells could thus mediate bi-directional communication between vessels and the nervous system, without the need for changes in vascular tone. This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder.
Topics: Animals; Brain; Cortical Spreading Depression; Humans; Meninges; Migraine Disorders; Vasodilation
PubMed: 27312704
DOI: 10.1016/j.neuroscience.2016.06.012 -
Nature Communications Jun 2020Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been...
Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.
Topics: Animals; Brain Injuries; Erythrocytes; Lymph Nodes; Lymphangiogenesis; Lymphatic System; Lymphatic Vessels; Male; Meninges; Meningitis; Mice; Mice, Inbred C57BL; Models, Animal; Neck; Subarachnoid Hemorrhage; Vascular Endothelial Growth Factor Receptor-3
PubMed: 32572022
DOI: 10.1038/s41467-020-16851-z -
Developmental Cell Apr 2023The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells....
The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and timing are largely unknown. Here, we show that mouse arachnoid barrier cell specification requires the repression of Wnt-β-catenin signaling and that constitutively active β-catenin can prevent its formation. We also show that the arachnoid barrier is functional prenatally and, in its absence, a small molecular weight tracer and the bacterium group B Streptococcus can cross into the CNS following peripheral injection. Acquisition of barrier properties prenatally coincides with the junctional localization of Claudin 11, and increased E-cadherin and maturation continues after birth, where postnatal expansion is marked by proliferation and re-organization of junctional domains. This work identifies fundamental mechanisms that drive arachnoid barrier formation, highlights arachnoid barrier fetal functions, and provides novel tools for future studies on CNS barrier development.
Topics: Mice; Animals; beta Catenin; Meninges; Arachnoid; Blood-Brain Barrier; Central Nervous System; Tight Junctions
PubMed: 36996816
DOI: 10.1016/j.devcel.2023.03.005 -
PloS One 2021Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for...
OBJECTIVES
Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis.
METHODOLOGY
Adult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed.
RESULTS
Out of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein).
CONCLUSION
CSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.
Topics: Adult; Biomarkers; Diagnosis, Differential; Female; Humans; Male; Meningitis, Bacterial; Meningitis, Viral
PubMed: 34115780
DOI: 10.1371/journal.pone.0251518 -
Immunologic Research Feb 2017Hypertrophic pachymeningitis (HP) is a rare disorder that causes thickening of the dura mater. Inflammatory lesions may be located in the cerebral or spinal dura mater... (Review)
Review
Hypertrophic pachymeningitis (HP) is a rare disorder that causes thickening of the dura mater. Inflammatory lesions may be located in the cerebral or spinal dura mater or, less frequently, in both locations simultaneously. Numerous clinico-pathological entities cause thickening of the pachymeninges. Indeed, HP is a potential manifestation of many different diseases, but the diagnosis often remains uncertain. Cases in which the pachymeningitis has no known aetiology are termed "idiopathic" HP (IHP). Recently, it has been suggested that IgG4-related disease represents a subset of cases previously diagnosed as idiopathic hypertrophic pachymeningitis. Little is known regarding the pathogenic events of IHP. In a general theory, the inflammatory infiltrate, mainly consisting of B and T lymphocytes, activates fibroblasts and induces collagen deposition, leading to tissue hypertrophy and increased dural thickness. Clinical manifestations of IHP depend upon the location of the inflammatory lesions and compression of the adjacent nervous structures. Three central pathological features are lymphoplasmacytic infiltration, obliterative phlebitis, and storiform fibrosis. MRI is the examination of choice for the preliminary diagnosis of IHP. Histopathological examination of a biopsy specimen of the dura mater would finally confirm the diagnosis. The differential diagnosis for HP is broad and includes infections, autoimmune disorders, and neoplasia. Currently, there is no consensus about treatment for patients with IHP. There is a preference for glucocorticoid treatment on diagnosis followed by the addition of other immunosuppressive agents in the event of a recurrence. Rituximab is used in patients who did not respond to glucocorticoids or to conventional steroid-sparing agents.
Topics: Autoimmune Diseases; Diagnosis, Differential; Humans; Hypertrophy; Immunoglobulin G; Meninges; Meningitis; Prognosis
PubMed: 27592235
DOI: 10.1007/s12026-016-8863-1 -
Seminars in Ultrasound, CT, and MR Oct 2023The spinal cord comprises the part of the central nervous system located within the vertebral canal, extending from the foramen magnum to approximately the second lumbar... (Review)
Review
The spinal cord comprises the part of the central nervous system located within the vertebral canal, extending from the foramen magnum to approximately the second lumbar vertebra. The spinal cord is covered by 3 meninges: dura mater, arachnoid mater, and pia mater (arranged from the outermost layer inward). A cross-section of the spinal cord reveals gray and white matter. Ascending and descending pathways have defined locations in the matter of the spinal cord. This article aims to review the spinal cord anatomy and demonstrate the imaging aspects, which are essential for the interpretation and understanding of spinal cord injuries.
Topics: Humans; Meninges; Dura Mater; Spinal Cord; Arachnoid; Pia Mater
PubMed: 37555687
DOI: 10.1053/j.sult.2023.03.011 -
British Journal of Hospital Medicine... Feb 2017
Topics: Adult; Anti-Bacterial Agents; Female; Humans; Meningism; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 28165786
DOI: 10.12968/hmed.2017.78.2.108