-
Nature Neuroscience Jul 2022The meninges, comprising the leptomeninges (pia and arachnoid layers) and the pachymeninx (dura layer), participate in central nervous system (CNS) autoimmunity, but...
The meninges, comprising the leptomeninges (pia and arachnoid layers) and the pachymeninx (dura layer), participate in central nervous system (CNS) autoimmunity, but their relative contributions remain unclear. Here we report on findings in animal models of CNS autoimmunity and in patients with multiple sclerosis, where, in acute and chronic disease, the leptomeninges were highly inflamed and showed structural changes, while the dura mater was only marginally affected. Although dural vessels were leakier than leptomeningeal vessels, effector T cells adhered more weakly to the dural endothelium. Furthermore, local antigen-presenting cells presented myelin and neuronal autoantigens less efficiently, and the activation of autoreactive T cells was lower in dural than leptomeningeal layers, preventing local inflammatory processes. Direct antigen application was required to evoke a local inflammatory response in the dura. Together, our data demonstrate an uneven involvement of the meningeal layers in CNS autoimmunity, in which effector T cell trafficking and activation are functionally confined to the leptomeninges, while the dura remains largely excluded from CNS autoimmune processes.
Topics: Animals; Arachnoid; Autoimmunity; Central Nervous System; Dura Mater; Humans; Meninges; Multiple Sclerosis
PubMed: 35773544
DOI: 10.1038/s41593-022-01108-3 -
Journal of Neuroinflammation May 2023The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an... (Review)
Review
The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an immunologically active site. Meningeal immunity has emerged as a key factor in modulating proper brain function and social behavior, performing constant immune surveillance of the CNS, and participating in several neurological diseases. However, it remains to be determined how meningeal immunity contributes to CNS physiology and pathophysiology. With the advances in single-cell omics, new approaches, such as single-cell technologies, unveiled the details of cellular and molecular mechanisms underlying meningeal immunity in CNS homeostasis and dysfunction. These new findings contradict some previous dogmas and shed new light on new possible therapeutic targets. In this review, we focus on the complicated multi-components, powerful meningeal immunosurveillance capability, and its crucial involvement in physiological and neuropathological conditions, as recently revealed by single-cell technologies.
Topics: Humans; Meninges; Central Nervous System; Nervous System Diseases
PubMed: 37231449
DOI: 10.1186/s12974-023-02803-z -
Immunity Jun 2017The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages,... (Review)
Review
The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages, as well as choroid plexus and meningeal macrophages, dendritic cells, and granulocytes. These myeloid populations enjoy an intimate relationship with the CNS, where they play an essential role in both health and disease. Although the importance of these cells is clearly recognized, their exact function in the CNS continues to be explored. Here, we review the subsets of myeloid cells that inhabit the parenchyma, meninges, and choroid plexus and discuss their roles in CNS homeostasis. We also discuss the role of these cells in various neurological pathologies, such as autoimmunity, mechanical injury, neurodegeneration, and infection. We highlight the neuroprotective nature of certain myeloid cells by emphasizing their therapeutic potential for the treatment of neurological conditions.
Topics: Animals; Autoimmune Diseases; Central Nervous System; Choroid Plexus; Humans; Infections; Meninges; Myeloid Cells; Neurodegenerative Diseases; Neuroimmunomodulation; Neuroprotection; Wounds and Injuries
PubMed: 28636961
DOI: 10.1016/j.immuni.2017.06.007 -
Immune-Mediated Hypertrophic Pachymeningitis and its Mimickers: Magnetic Resonance Imaging Findings.Academic Radiology Nov 2023Hypertrophic pachymeningitis (HP) is a rare and chronic inflammatory disorder presenting as localized or diffuse thickening of the dura mater. It can be idiopathic or an... (Review)
Review
Hypertrophic pachymeningitis (HP) is a rare and chronic inflammatory disorder presenting as localized or diffuse thickening of the dura mater. It can be idiopathic or an unusual manifestation of immune-mediated, infectious, and neoplastic conditions. Although some cases may remain asymptomatic, HP can lead to progressive headaches, cranial nerve palsies, hydrocephalus, and other neurological complications, which makes its recognition a fundamental step for prompt treatment. Regarding the diagnosis workup, enhanced MRI is the most useful imaging method to evaluate dural thickening. This article addresses the MR imaging patterns of immune-mediated HP, including immunoglobulin G4-related disease, neurosarcoidosis, granulomatosis with polyangiitis, rheumatoid pachymeningitis, and idiopathic HP. The main infectious and neoplastic mimicking entities are also discussed with reference to conventional and advanced MR sequences.
Topics: Humans; Diagnosis, Differential; Dura Mater; Hypertrophy; Magnetic Resonance Imaging; Meningitis
PubMed: 36882352
DOI: 10.1016/j.acra.2023.01.017 -
Current Opinion in Immunology Jun 2022The meninges encase the brain and spinal cord and house a variety of immune cells, including developing and mature B cells, and antibody-secreting plasma cells. In... (Review)
Review
The meninges encase the brain and spinal cord and house a variety of immune cells, including developing and mature B cells, and antibody-secreting plasma cells. In homeostasis, these cells localize around the dural venous sinuses, providing a defense 'zone' to protect the brain and spinal cord from blood-borne pathogens. Dural plasma cells predominantly secrete IgA antibodies, and some originate from the gastrointestinal tract, with the number and antibody isotype shaped by the gut microbiome. For developing B cells arriving from the adjacent bone marrow, the dura provides a site to tolerize against central nervous system antigens. In this review, we will discuss our current understanding of meningeal humoral immunity in homeostasis.
Topics: Brain; Dura Mater; Homeostasis; Humans; Immunity, Humoral; Meninges
PubMed: 35569417
DOI: 10.1016/j.coi.2022.102188 -
Neuroimaging Clinics of North America Aug 2022The ventricular system, subarachnoid spaces, and meninges are structures that lend structure, support, and protection to the brain and spinal cord. This article provides... (Review)
Review
The ventricular system, subarachnoid spaces, and meninges are structures that lend structure, support, and protection to the brain and spinal cord. This article provides a detailed look at the anatomy of the intracranial portions of these structures with a particular focus on neuroimaging methods.
Topics: Brain; Humans; Meninges; Spinal Cord; Subarachnoid Space
PubMed: 35843664
DOI: 10.1016/j.nic.2022.04.005 -
Current Opinion in Hematology May 2022The recent (re)discovery of the meningeal lymphatic has brought a new player in brain neurophysiology. This review highlights the state of the current research on the... (Review)
Review
PURPOSE OF REVIEW
The recent (re)discovery of the meningeal lymphatic has brought a new player in brain neurophysiology. This review highlights the state of the current research on the meningeal lymphatic vasculature, from its specific physiology to its increasing implication in normal and pathological brain function.
RECENT FINDINGS
Growing evidence are emerging about the uniqueness of the meningeal lymphatic vasculature and its implication in multiple neurological and neurotraumatic disorders.
SUMMARY
These studies are highlighting a new and unexpected role for the lymphatic vasculature in brain function and a potential new therapeutic target for neurological disorders.
Topics: Brain; Humans; Lymphatic System; Lymphatic Vessels; Meninges
PubMed: 35441600
DOI: 10.1097/MOH.0000000000000711 -
Fluids and Barriers of the CNS Dec 2023Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the...
Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the brain is based on postmortem macroscopic examination. Ultrastructural and single cell transcriptome analyses have documented that the 3 meningeal layers can be subdivided into several distinct layers based on cellular characteristics. We here re-examined the existence of a 4 meningeal membrane, Subarachnoid Lymphatic-like Membrane or SLYM in Prox1-eGFP reporter mice. Imaging of freshly resected whole brains showed that SLYM covers the entire brain and brain stem and forms a roof shielding the subarachnoid cerebrospinal fluid (CSF)-filled cisterns and the pia-adjacent vasculature. Thus, SLYM is strategically positioned to facilitate periarterial influx of freshly produced CSF and thereby support unidirectional glymphatic CSF transport. Histological analysis showed that, in spinal cord and parts of dorsal cortex, SLYM fused with the arachnoid barrier layer, while in the basal brain stem typically formed a 1-3 cell layered membrane subdividing the subarachnoid space into two compartments. However, great care should be taken when interpreting the organization of the delicate leptomeningeal membranes in tissue sections. We show that hyperosmotic fixatives dehydrate the tissue with the risk of shrinkage and dislocation of these fragile membranes in postmortem preparations.
Topics: Mice; Animals; Meninges; Dura Mater; Arachnoid; Subarachnoid Space; Cerebral Cortex
PubMed: 38098084
DOI: 10.1186/s12987-023-00500-w -
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 -
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