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Cell Reports Nov 2022The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal...
The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-related pain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.
Topics: Animals; Mice; Meninges; Neurons, Afferent; Headache; Locomotion
PubMed: 36384109
DOI: 10.1016/j.celrep.2022.111648 -
Cancer Treatment Reviews Apr 1999Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. This disorder is being diagnosed with increasing frequency as patients live longer and... (Review)
Review
Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. This disorder is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. The most common cancers to involve the leptomeninges are breast cancer, lung cancer, and melanomas. Tumour cells reach the leptominges by hematogenous spread or by direct extension from pre-existing lesions and are then disseminated throughout the neuroaxis by the flow of the cerebrospinal fluid. Patients present with signs and symptoms from injury to nerves that traverse the subarachnoid space, direct tumour invasion into the brain or spinal cord, alterations in blood supply to the nervous system, obstruction of normal cerebrospinal fluid (CSF) flow pathways, or general interference with brain function. The diagnosis is most commonly made by lumbar puncture although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis. Radiologic studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges, or hydrocephalus without a mass lesion. Without treatment, the median survival of patients with this disorder is 4-6 weeks and death occurs from progressive neurologic dysfunction. Early diagnosis and therapy is critical to preserving neurologic function. Radiation therapy to symptomatic sites and disease visible on neuroimaging studies and intrathecal chemotherapy increases the median survival to 3-6 months. The major favorable prognostic factors include excellent performance status, absence of serious fixed neurologic deficits, normal CSF flow scans, and absent or responsive systemic tumour. Aggressive therapy for this disorder is often accompanied by a necrotizing leukoencephalopathy which becomes symptomatic months after treatment with radiation and intrathecal methotrexate. As currently available therapies are toxic and provide limited benefits, novel approaches are being studied. Further information on the mechanisms of neurotoxicity from antineoplastic agents is critical to providing better outcomes for this increasing common complication of cancer.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma; Combined Modality Therapy; Diagnosis, Differential; Diagnostic Imaging; Humans; Meningeal Neoplasms; Meningitis
PubMed: 10395835
DOI: 10.1053/ctrv.1999.0119 -
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 -
Cancer Imaging : the Official... Oct 2009Primary malignant tumours arising from the meninges are distinctly uncommon, and when they occur, they are usually sarcomas. In contrast, metastatic meningeal... (Review)
Review
Primary malignant tumours arising from the meninges are distinctly uncommon, and when they occur, they are usually sarcomas. In contrast, metastatic meningeal involvement is increasingly seen as advances in cancer therapy have changed the natural history of malignant disease and prolonged the life span of cancer patients. The meninges can either be infiltrated by contiguous extension of primary tumours of the central nervous system, paranasal sinuses and skull base origin or can be diffusely infiltrated from haematogenous dissemination from distant primary malignancies. Imaging in these patients provides crucial information in planning management. This article reviews the pertinent anatomy that underlies imaging findings, discusses the mechanism of meningeal metastasis and highlights different imaging patterns of meningeal carcinomatosis and the pitfalls.
Topics: Cerebral Infarction; Contrast Media; Diagnosis, Differential; False Positive Reactions; Humans; Leukemic Infiltration; Magnetic Resonance Imaging; Meningeal Carcinomatosis; Meningeal Neoplasms; Meninges; Sarcoma; Ventriculoperitoneal Shunt
PubMed: 19965290
DOI: 10.1102/1470-7330.2009.9004 -
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 -
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 -
Chinese Clinical Oncology Jun 2015Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated... (Review)
Review
Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.
Topics: Animals; Combined Modality Therapy; Humans; Meningeal Carcinomatosis; Meningitis; Neuroimaging; Patient Selection; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 26112812
DOI: 10.3978/j.issn.2304-3865.2015.05.02 -
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 -
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 -
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