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Biomolecules May 2022There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main... (Review)
Review
There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main contributor to VCI. Several potential physiopathologic mechanisms have been proven to be involved in the process of CSVD, such as blood-brain barrier damage, small vessels stiffening, venous collagenosis, cerebral blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin damage, and subsequent neurodegeneration. However, there still is a limited overall understanding of the sequence and the relative importance of these mechanisms. The glymphatic system (GS) and meningeal lymphatic vessels (mLVs) are the analogs of the lymphatic system in the central nervous system (CNS). As such, these systems play critical roles in regulating cerebrospinal fluid (CSF) and interstitial fluid (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence has suggested that the glymphatic and meningeal lymphatic vessels played vital roles in animal models of CSVD and patients with CSVD. Given the complexity of CSVD, it was significant to understand the underlying interaction between glymphatic and meningeal lymphatic transport with CSVD. Here, we provide a novel framework based on new advances in main four aspects, including vascular risk factors, potential mechanisms, clinical subtypes, and cognition, which aims to explain how the glymphatic system and meningeal lymphatic vessels contribute to the progression of CSVD and proposes a comprehensive insight into the novel therapeutic strategy of CSVD.
Topics: Animals; Brain; Central Nervous System; Cerebral Small Vessel Diseases; Glymphatic System; Humans; Lymphatic System; Meninges
PubMed: 35740873
DOI: 10.3390/biom12060748 -
Nature Immunology Dec 2022Increasing evidence indicates close interaction between immune cells and the brain, revising the traditional view of the immune privilege of the brain. However, the...
Increasing evidence indicates close interaction between immune cells and the brain, revising the traditional view of the immune privilege of the brain. However, the specific mechanisms by which immune cells promote normal neural function are not entirely understood. Mucosal-associated invariant T cells (MAIT cells) are a unique type of innate-like T cell with molecular and functional properties that remain to be better characterized. In the present study, we report that MAIT cells are present in the meninges and express high levels of antioxidant molecules. MAIT cell deficiency in mice results in the accumulation of reactive oxidative species in the meninges, leading to reduced expression of junctional protein and meningeal barrier leakage. The presence of MAIT cells restricts neuroinflammation in the brain and preserves learning and memory. Together, our work reveals a new functional role for MAIT cells in the meninges and suggests that meningeal immune cells can help maintain normal neural function by preserving meningeal barrier homeostasis and integrity.
Topics: Animals; Mice; Mucosal-Associated Invariant T Cells; Brain; Meninges; Cognition; Oxidative Stress
PubMed: 36411380
DOI: 10.1038/s41590-022-01349-1 -
Journal of Clinical Virology : the... Sep 2017Aseptic meningitis represents a common diagnostic and management dilemma to clinicians.
BACKGROUND
Aseptic meningitis represents a common diagnostic and management dilemma to clinicians.
OBJECTIVES
To compare the clinical epidemiology, diagnostic evaluations, management, and outcomes between adults and children with aseptic meningitis.
STUDY DESIGN
We conducted a retrospective study from January 2005 through September 2010 at 9 Memorial Hermann Hospitals in Houston, TX. Patients age≥2months who presented with community-acquired aseptic meningitis with a CSF white blood cell count >5cells/mm and a negative Gram stain and cultures were enrolled. Patients with a positive cryptococcal antigen, positive blood cultures, intracranial masses, brain abscesses, or encephalitis were excluded.
RESULTS
A total of 509 patients were included; 404 were adults and 105 were children. Adults were most likely to be female, Caucasian, immunosuppressed, have meningeal symptoms (headache, nausea, stiff neck, photophobia) and have a higher CSF protein (P <0.05). In contrast, children were more likely to have respiratory symptoms, fever, and leukocytosis (P <0.05). In 410 (81%) patients, the etiologies remained unknown. Adults were more likely to be tested for and to have Herpes simplex virus and West Nile virus while children were more likely to be tested for and to have Enterovirus (P <0.001). The majority of patients were admitted (96.5%) with children receiving antibiotic therapy more frequently (P <0.001) and adults receiving more antiviral therapy (P=0.001). A total of 384 patients (75%) underwent head CT scans and 125 (25%) MRI scans; all were normal except for meningeal enhancement. All patients had a good clinical outcome at discharge.
DISCUSSION
Aseptic meningitis in adults and children represent a management challenge as etiologies remained unknown for the majority of patients due to underutilization of currently available diagnostic techniques.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Meningitis, Aseptic; Middle Aged; Retrospective Studies; Texas; Young Adult
PubMed: 28806629
DOI: 10.1016/j.jcv.2017.07.016 -
Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630 -
Magnetic Resonance in Medical Sciences... Mar 2022The central nervous system (CNS) was previously thought to be the only organ system lacking lymphatic vessels to remove waste products from the interstitial space.... (Review)
Review
The central nervous system (CNS) was previously thought to be the only organ system lacking lymphatic vessels to remove waste products from the interstitial space. Recently, based on the results from animal experiments, the glymphatic system was hypothesized. In this hypothesis, cerebrospinal fluid (CSF) enters the periarterial spaces, enters the interstitial space of the brain parenchyma via aquaporin-4 (AQP4) channels in the astrocyte end feet, and then exits through the perivenous space, thereby clearing waste products. From the perivenous space, the interstitial fluid drains into the subarachnoid space and meningeal lymphatics of the parasagittal dura. It has been reported that the glymphatic system is particularly active during sleep. Impairment of glymphatic system function might be a cause of various neurodegenerative diseases such as Alzheimer's disease, normal pressure hydrocephalus, glaucoma, and others. Meningeal lymphatics regulate immunity in the CNS. Many researchers have attempted to visualize the function and structure of the glymphatic system and meningeal lymphatics in vivo using MR imaging. In this review, we aim to summarize these in vivo MR imaging studies and discuss the significance, current limitations, and future directions. We also discuss the significance of the perivenous cyst formation along the superior sagittal sinus, which is recently discovered in the downstream of the glymphatic system.
Topics: Animals; Brain; Central Nervous System; Glymphatic System; Magnetic Resonance Imaging; Meninges
PubMed: 33250472
DOI: 10.2463/mrms.rev.2020-0122 -
Annual Review of Neuroscience Jul 2023Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the... (Review)
Review
Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the trigeminal nerve. Electrical or mechanical stimulation of this nerve surrounding large blood vessels evokes headache patterns as in migraine, and the brain, blood, and meninges are likely sources of headache triggers. Cerebrospinal fluid may play a significant role in migraine by transferring signals released from the brain to overlying pain-sensitive meningeal tissues, including dura mater. Interactions between trigeminal afferents, neuropeptides, and adjacent meningeal cells and tissues cause neurogenic inflammation, a critical target for current prophylactic and abortive migraine therapies. Here we review the importance of the cranial meninges to migraine headaches, explore the properties of trigeminal meningeal afferents, and briefly review emerging concepts, such as meningeal neuroimmune interactions, that may one day prove therapeutically relevant.
Topics: Humans; Migraine Disorders; Meninges; Dura Mater; Headache; Brain
PubMed: 36913712
DOI: 10.1146/annurev-neuro-080422-105509 -
Medecine Et Sante Tropicales Feb 2018Angiostrongyliasis, the leading cause worldwide of eosinophilic meningitis, is an emergent disease due to Angiostrongylus cantonensis larvae, transmitted accidentally to... (Review)
Review
Angiostrongyliasis, the leading cause worldwide of eosinophilic meningitis, is an emergent disease due to Angiostrongylus cantonensis larvae, transmitted accidentally to humans. Contamination of children usually occurs by direct contact with an infected mollusk. Eosinophilic meningoencephalitis is the major clinical feature of this parasitic infection in humans. It is usually benign for adults, but more severe for children. Clinical symptoms usually combine fever, meningitis, and neurological signs (somnolence, moaning, hypotonia, convulsions, and increased intracranial pressure). Presumptive diagnosis of human angiostrongyliasis is based on epidemiologic characteristics, clinical symptoms, medical history, and laboratory findings, in particular, hypereosinophilia in blood and cerebrospinal fluid. Treatment is based on corticosteroids associated with anthelmintics. This work reviews the diagnosis and treatment of this life-threatening (especially in children) parasitic disease and the need for preventive action.
Topics: Child; Humans; Meningitis; Strongylida Infections
PubMed: 29616650
DOI: 10.1684/mst.2018.0756 -
Genome Medicine May 2022Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role....
BACKGROUND
Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples.
METHODS
Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers.
RESULTS
In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples.
CONCLUSIONS
Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura.
Topics: Animals; Endothelial Cells; Humans; Immunity; Meningeal Neoplasms; Meninges; Meningioma; Mice; Tumor Microenvironment
PubMed: 35534852
DOI: 10.1186/s13073-022-01051-9 -
Neuron Nov 2022In an interview with Neuron, Jony Kipnis discusses his formative academic years and subsequent discoveries in meningeal lymphatics. He is enthusiastic about the prospect...
In an interview with Neuron, Jony Kipnis discusses his formative academic years and subsequent discoveries in meningeal lymphatics. He is enthusiastic about the prospect of therapeutic developments in neuroimmunology arising from focusing on the brain's borders.
Topics: Humans; Male; Lymphatic System; Meninges
PubMed: 36327892
DOI: 10.1016/j.neuron.2022.10.010 -
The Journal of Experimental Medicine Jul 2023The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in...
The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer's disease, impaired meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins in the CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, the mechanisms underlying this decline remain elusive. Here, we demonstrate that age-related alterations in meningeal immunity underlie this lymphatic impairment. Single-cell RNA sequencing of meningeal lymphatic endothelial cells from aged mice revealed their response to IFNγ, which was increased in the aged meninges due to T cell accumulation. Chronic elevation of meningeal IFNγ in young mice via AAV-mediated overexpression attenuated CSF drainage-comparable to the deficits observed in aged mice. Therapeutically, IFNγ neutralization alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable approach to normalize CSF drainage and alleviate the neurological deficits associated with impaired waste removal.
Topics: Mice; Animals; Endothelial Cells; Central Nervous System; Meninges; Lymphatic Vessels; Alzheimer Disease; Lymphatic System; Brain
PubMed: 37027179
DOI: 10.1084/jem.20221929