-
Journal of Immunology (Baltimore, Md. :... Jan 2020At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding... (Review)
Review
At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding the CNS host diverse populations of immune cells that influence how CNS-related immune responses develop. Interstitial and cerebrospinal fluid produced in the CNS is continuously drained, and recent advances have emphasized that this process is largely taking place through the lymphatic system. To what extent this fluid process mobilizes CNS-derived Ags toward meningeal immune cells and subsequently the peripheral immune system through the lymphatic vessel network is a question of significant clinical importance for autoimmunity, tumor immunology, and infectious disease. Recent advances in understanding the role of meningeal lymphatics as a communicator between the brain and peripheral immunity are discussed in this review.
Topics: Animals; Brain; Central Nervous System; Humans; Immunologic Surveillance; Lymphatic Vessels; Meninges
PubMed: 31907271
DOI: 10.4049/jimmunol.1900838 -
Neurology Jul 2015To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated...
OBJECTIVE
To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.
METHODS
Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination.
RESULTS
Focal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination.
CONCLUSION
Leptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.
Topics: Gadolinium; Humans; Magnetic Resonance Imaging; Meninges; Meningitis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 25888557
DOI: 10.1212/WNL.0000000000001587 -
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 -
Current Opinion in Genetics &... Jun 2011The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that... (Review)
Review
The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that the fetal meninges play important roles during brain development. Through the release of diffusible factors, the meninges influence the proliferative and migratory behaviors of neural progenitors and neurons in the forebrain and hindbrain. Meningeal cells also secrete and organize the pial basement membrane (BM), a critical anchor point for the radially oriented fibers of neuroepithelial stem cells. With its emerging role in brain development, the potential that defects in meningeal development may underlie certain congenital brain abnormalities in humans should be considered. In this review, we will discuss what is known about assembly of the fetal meninges and review the role of meningeal-derived proteins in mouse and human brain development.
Topics: Animals; Brain; Female; Fetus; Humans; Meninges; Mice; Neurons
PubMed: 21251809
DOI: 10.1016/j.gde.2010.12.005 -
BMC Neurology Mar 2012Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established... (Review)
Review
Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.
Topics: Cerebral Cortex; Humans; Inflammation; Meninges; Multiple Sclerosis
PubMed: 22397318
DOI: 10.1186/1471-2377-12-11 -
PloS One 2017We undertook a systematic review and meta-analysis to address the question "what is the impact of meningitis on IQ and development." (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We undertook a systematic review and meta-analysis to address the question "what is the impact of meningitis on IQ and development."
METHODS
Search: conducted using standardized search terms across Medline, PsychInfo and EMBASE to 06/2014. Eligibility: human studies of any infectious aetiology of meningitis reporting IQ or infant developmental age or stage outcomes. Quality: Centre for Evidence Based Medicine, Oxford, quality tools. Analysis: random effects meta-analysis by organism.
RESULTS
39 studies were included in the review, 34 providing data on IQ (2015 subjects) and 12 on developmental delay (382 subjects). Across all bacterial organisms, meningitis survivors had a mean IQ 5.50 (95% CI: -7.19, -3.80; I2 = 47%, p = 0.02) points lower than controls. IQ was significantly lower than controls for Neisseria meningitides (NM: 5 points) and Haemophilus influenzae b (Hib: 6 points) but not in viral meningitis, with only single studies included for Streptococcus pneumoniae (SP) and group B streptococcus (GBS). The pooled relative risk (RR) for low IQ (IQ<70) in survivors of bacterial meningitis compared with controls was 4.99 (95% CI: 3.17, 7.86) with no significant heterogeneity (I2 = 49%, p = 0.07). Developmental delay of approximately 0.5SD was reported in studies of bacterial meningitis but no delay in the only study of viral meningitis.
CONCLUSIONS
We found moderate evidence that surviving bacterial meningitis has a deleterious impact on IQ and development but no evidence that viral meningitis had meaningful cognitive impacts. Survivors of bacterial meningitis should be routinely offered screening for cognitive deficits and developmental delay in addition to hearing loss.
Topics: Humans; Intelligence; Meningitis, Bacterial; Meningitis, Viral
PubMed: 28837564
DOI: 10.1371/journal.pone.0175024 -
Fluids and Barriers of the CNS Feb 2023The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic...
BACKGROUND
The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal fluid-filled subarachnoid space and across the brain parenchyma via their connection to glymphatic structures. Meningeal fibroblasts lining and traversing the subarachnoid space have direct impact on the composition of the cerebrospinal fluid through endocytotic uptake as well as extensive protein secretion. In addition, the meninges are an active site for immunological processes and act as gatekeeper for immune cells entering the brain. During aging in mice, lymphatic drainage from the brain is less efficient contributing to neurodegenerative processes. Aging also affects the immunological status of the meninges, with increasing numbers of T cells, changing B cell make-up, and altered macrophage complement.
METHODS
We employed RNASeq to measure gene expression and to identify differentially expressed genes in meninges isolated from young and aged mice. Using Ingenuity pathway, GO term, and MeSH analyses, we identified regulatory pathways and cellular functions in meninges affected by aging.
RESULTS
Aging had profound impact on meningeal gene expression. Pathways related to innate as well as adaptive immunity were affected. We found evidence for increasing numbers of T and B lymphocytes and altered activity profiles for macrophages and other myeloid cells. Furthermore, expression of pro-inflammatory cytokine and chemokine genes increased with aging. Similarly, the complement system seemed to be more active in meninges of aged mice. Altered expression of solute carrier genes pointed to age-dependent changes in cerebrospinal fluid composition. In addition, gene expression for secreted proteins showed age-dependent changes, in particular, genes related to extracellular matrix composition and organization were affected.
CONCLUSIONS
Aging has profound effects on meningeal gene expression; thereby affecting the multifaceted functions meninges perform to maintain the homeostasis of the central nervous system. Thus, age-dependent neurodegenerative processes and cognitive decline are potentially in part driven by altered meningeal function.
Topics: Mice; Animals; Meninges; Central Nervous System; Brain; Aging; Gene Expression
PubMed: 36747230
DOI: 10.1186/s12987-023-00412-9 -
Cells Dec 2021The recent (re)discovery of the meningeal lymphatic system has opened new theories as to how immune cells traffic and interact with the central nervous system (CNS).... (Review)
Review
The recent (re)discovery of the meningeal lymphatic system has opened new theories as to how immune cells traffic and interact with the central nervous system (CNS). While evidence is accumulating on the contribution of the meningeal lymphatic system in both homeostatic and disease conditions, a lot remains unknown about the mechanisms that allow for interaction between the meningeal lymphatic system and immune cells. In this review, we synthesize the knowledge about the lymphatic immune interaction in the CNS and highlight the important questions that remain to be answered.
Topics: Animals; Cell Movement; Homeostasis; Humans; Leukocytes; Lymphatic Vessels; Meninges; Phenotype
PubMed: 34943894
DOI: 10.3390/cells10123385 -
Journal of Neurology, Neurosurgery, and... Feb 1990Five patients with chronic arachnoiditis and syringomyelia were studied. Three patients had early life meningitis and developed symptoms of syringomyelia eight, 21, and...
Five patients with chronic arachnoiditis and syringomyelia were studied. Three patients had early life meningitis and developed symptoms of syringomyelia eight, 21, and 23 years after the acute infection. One patient had a spinal dural thoracic AVM and developed a thoracic syrinx 11 years after spinal subarachnoid haemorrhage and five years after surgery on the AVM. A fifth patient had tuberculous meningitis with transient spinal cord dysfunction followed by development of a lumbar syrinx seven years later. Arachnoiditis can cause syrinx formation by obliterating the spinal vasculature causing ischaemia. Small cystic regions of myelomalacia coalesce to form cavities. In other patients, central cord ischaemia mimics syringomyelia but no cavitation is present. Scar formation with spinal block leads to altered dynamics of cerebrospinal fluid (CSF) flow and contributes to the formation of spinal cord cystic cavities.
Topics: Adult; Aged; Aged, 80 and over; Arachnoid; Arachnoiditis; Atrophy; Cicatrix; Dura Mater; Female; Follow-Up Studies; Humans; Intracranial Arteriovenous Malformations; Male; Meningitis; Middle Aged; Postoperative Complications; Spinal Cord; Syringomyelia; Tissue Adhesions
PubMed: 2313296
DOI: 10.1136/jnnp.53.2.106 -
Clinical Microbiology Reviews Apr 1993Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial... (Review)
Review
Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.
Topics: Animals; Bacteremia; Blood-Brain Barrier; Cerebrovascular Circulation; Disease Models, Animal; Humans; Intracranial Pressure; Lipopolysaccharides; Meningitis, Bacterial; Subarachnoid Space
PubMed: 8472245
DOI: 10.1128/CMR.6.2.118