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Neuromolecular Medicine Sep 2021Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with... (Review)
Review
Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with cerebrospinal fluid. During development, the meninges is formed by both mesenchymal and neural crest cells. There is now emerging evidence that subsets of undifferentiated stem cells might persist in the adult meninges. In this mini-review, we survey representative studies of brain-meningeal interactions and discuss the hypothesis that the meninges are not just protective membranes, but instead contain multiplex stem cell subsets that may contribute to central nervous system (CNS) homeostasis. Further investigations into meningeal multipotent cells may reveal a "hidden" target for promoting neurovascular remodeling and repair after CNS injury and disease.
Topics: Adapalene; Adult Stem Cells; Animals; Brain Ischemia; Central Nervous System; Central Nervous System Diseases; Glymphatic System; Homeostasis; Humans; Male; Meninges; Multipotent Stem Cells; Neural Crest; Neural Stem Cells; Rats; Rats, Sprague-Dawley; Regeneration
PubMed: 33893971
DOI: 10.1007/s12017-021-08663-1 -
Neurology India 2022Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve... (Observational Study)
Observational Study
BACKGROUND
Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve palsies, and other focal neurological deficits. Two forms exist, one is primary, where all other causes have been excluded and the other is secondary where an identifiable cause exists. It is important to recognize these secondary causes as treatment depends on the etiology.
OBJECTIVE
To elucidate the various characteristics of HPM. To delineate clinical-radiological features that help differentiate secondary from primary causes and to understand treatment response and disease outcomes of HPM.
METHODS
This retrospective observational study included 33 patients who presented with radiological diagnosis of HPM from January 2014 to July 2019. Spontaneous intracranial hypotension patients were excluded. All patients were extensively evaluated for secondary causes and treatment outcomes were analyzed on follow-up.
RESULTS AND CONCLUSIONS
Secondary causes of HPM were present in 48% cases. The clue for primary causes is an associated Tolosa-Hunt syndrome. Secondary causes in our series are immunological, infection, and malignancy. Clues to differentiate primary from these secondary causes are clinical like myelopathy, seizures, poor response to immunosuppression; radiological like hypertrophic cranial nerves, infarcts, bony erosion, and leptomeningeal involvement. There are case reports in literature but large Indian studies are lacking. This manuscript presents a large cohort of cases with HPM, which helps differentiate primary from secondary causes, as management and prognosis depend on etiology. An algorithm depicting the approach to the management of HPM has been presented.
Topics: Humans; Magnetic Resonance Imaging; Meningitis; Cranial Nerve Diseases; Headache; Treatment Outcome; Hypertrophy; Dura Mater
PubMed: 36537427
DOI: 10.4103/0028-3886.364052 -
Cellular and Molecular Life Sciences :... Oct 2023Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune... (Review)
Review
Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune trafficking. Although these vessels were overlooked for centuries, they have now been characterized in humans, non-human primates, and rodents. Recent studies in mice have explored the stereotyped growth and expansion of MLVs in dura mater, the various transcriptional, signaling, and environmental factors regulating their development and long-term maintenance, and the pathological changes these vessels undergo in injury, disease, or with aging. Key insights gained from these studies have also been leveraged to develop therapeutic approaches that help augment or restore MLV functions to improve brain health and cognition. Here, we review fundamental processes that control the development of peripheral lymphatic networks and how these might apply to the growth and expansion of MLVs in their unique meningeal environment. We also emphasize key findings in injury and disease models that may reveal additional insights into the plasticity of these vessels throughout the lifespan. Finally, we highlight unanswered questions and future areas of study that can further reveal the exciting therapeutic potential of meningeal lymphatics.
Topics: Mice; Animals; Lymphatic Vessels; Meninges; Central Nervous System; Lymphatic System; Models, Animal
PubMed: 37872442
DOI: 10.1007/s00018-023-04984-5 -
Cancer Control : Journal of the Moffitt... Jan 2017Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia. (Review)
Review
BACKGROUND
Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia.
METHODS
The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of leukemic and lymphomatous meningitis.
RESULTS
Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease. Intrathecal and systemic chemotherapy remain the main therapeutic approaches for this disease. Outcomes have improved in patients with primary CNS lymphoma and meningeal involvement.
CONCLUSIONS
Appropriate selection of patients at high risk for leukemic and lymphomatous meningitis is important so that preventive strategies can decrease the incidence of this complication of leukemia and lymphoma. Use of chemotherapy agents that cross the blood-brain barrier and the adoption of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have increased the proportion of patients whose primary disease is cured.
Topics: Disease Management; Humans; Leukemia; Lymphoma; Meningitis; Prognosis
PubMed: 28178710
DOI: 10.1177/107327481702400105 -
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 -
Progress in Neurobiology Sep 2017Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of... (Review)
Review
Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of disease. Most basic research on the meninges and the neural brain is now done on mice, major attractions being the availability of reporter mice with fluorescent cells, and of a huge range of antibodies useful for immunocytochemistry and the characterization of isolated cells. In addition, two-photon microscopy through the unperforated calvaria allows intravital imaging of the undisturbed meninges with sub-micron resolution. The anatomy of the dorsal meninges of the mouse (and, indeed, of all mammals) differs considerably from that shown in many published diagrams: over cortical convexities, the outer layer, the dura, is usually thicker than the inner layer, the leptomeninx, and both layers are richly vascularized and innervated, and communicate with the lymphatic system. A membrane barrier separates them and, in disease, inflammation can be localized to one layer or the other, so experimentalists must be able to identify the compartment they are studying. Here, we present current knowledge of the functional anatomy of the meninges, particularly as it appears in intravital imaging, and review their role as a gateway between the brain, blood, and lymphatics, drawing on information that is scattered among works on different pathologies.
Topics: Allergy and Immunology; Animals; Brain; Intravital Microscopy; Meninges; Mice
PubMed: 28552391
DOI: 10.1016/j.pneurobio.2017.05.002 -
Immunology Nov 2021Ectopic lymphoid follicles (ELFs), resembling germinal centre-like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be... (Review)
Review
Ectopic lymphoid follicles (ELFs), resembling germinal centre-like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be found in the meninges of around 40% of the investigated progressive multiple sclerosis (MS) post-mortem brain tissues and are associated with the severity of cortical degeneration and clinical disease progression. Of predominant importance for progressive neuronal damage during the progressive MS phase appears to be meningeal inflammation, comprising diffuse meningeal infiltrates, B-cell aggregates and compartmentalized ELFs. However, the absence of a uniform definition of ELFs impedes reproducible and comparable neuropathological research in this field. In this review article, we will first highlight historical aspects and milestones around the discovery of ELFs in the meninges of progressive MS patients. In the next step, we discuss how animal models may contribute to an understanding of the mechanisms underlying ELF formation. Finally, we summarize challenges in investigating ELFs and propose potential directions for future research.
Topics: Animals; B-Lymphocytes; Disease Models, Animal; Humans; Meninges; Multiple Sclerosis, Chronic Progressive; Tertiary Lymphoid Structures
PubMed: 34293193
DOI: 10.1111/imm.13395 -
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 -
Methods (San Diego, Calif.) Aug 2017A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain... (Review)
Review
A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx.
Topics: Animals; Dendritic Cells; Host-Pathogen Interactions; Intravital Microscopy; Lymphocytic choriomeningitis virus; Macrophages; Meninges; Meningitis; Mice; Mice, Transgenic; Microorganisms, Genetically-Modified; Microscopy, Fluorescence, Multiphoton; Neutrophils; Plasmodium berghei; T-Lymphocytes; Trypanosoma brucei brucei
PubMed: 28351758
DOI: 10.1016/j.ymeth.2017.03.020