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ELife Jan 2023Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about...
Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.
Topics: Mice; Animals; Brain Injuries, Traumatic; Brain Concussion; Brain Injuries; Aging; Meninges; Mice, Inbred C57BL; Microglia; Brain; Disease Models, Animal
PubMed: 36594818
DOI: 10.7554/eLife.81154 -
Brain and Nerve = Shinkei Kenkyu No... May 2021Rheumatoid meningitis, a central nervous system complication of rheumatoid arthritis, has low morbidity but poor prognosis without treatment. Contrast-enhanced meningeal...
Rheumatoid meningitis, a central nervous system complication of rheumatoid arthritis, has low morbidity but poor prognosis without treatment. Contrast-enhanced meningeal lesions on one side of the brain on MRI and hyperintensity of the pia mater on FLAIR image are characteristic features and should trigger the suspicion of rheumatoid meningitis. Steroids are effective for treatment, and good outcomes can be obtained through early diagnosis and intervention.
Topics: Arthritis, Rheumatoid; Brain; Humans; Magnetic Resonance Imaging; Meningitis
PubMed: 34006686
DOI: 10.11477/mf.1416201796 -
World Neurosurgery May 2020Rheumatoid meningitis is a rare manifestation of autoimmune rheumatoid arthritis.
BACKGROUND
Rheumatoid meningitis is a rare manifestation of autoimmune rheumatoid arthritis.
CASE DESCRIPTION
A 70-year-old man with rheumatoid arthritis had presented with speech difficulties and limb weakness. Magnetic resonance imaging of his brain demonstrated diffuse meningeal enhancement. A biopsy confirmed the presence of rheumatoid meningitis.
CONCLUSION
In the present report, we have discussed the diagnostic and therapeutic approach to rheumatoid meningitis.
Topics: Aged; Arthritis, Rheumatoid; Biopsy; Brain; Humans; Magnetic Resonance Imaging; Male; Meningitis
PubMed: 32035199
DOI: 10.1016/j.wneu.2020.01.220 -
Clinica Chimica Acta; International... Aug 2023Meningitis is defined as the inflammation of the meninges that is most often caused by various bacterial and viral pathogens, and is associated with high rates of... (Review)
Review
Meningitis is defined as the inflammation of the meninges that is most often caused by various bacterial and viral pathogens, and is associated with high rates of mortality and morbidity. Early detection of bacterial meningitis is essential to appropriate antibiotic therapy. Alterations in immunologic biomarkers levels have been considered the diagnostic approach in medical laboratories for the identifying of infections. The early increasing immunologic mediators such as cytokines and acute phase proteins (APPs) during bacterial meningitis have made they significant indicators for laboratory diagnosis. Immunology biomarkers showed wide variable sensitivity and specificity values that influenced by different reference values, selected a certain cutoff point, methods of detection, patient characterization and inclusion criteria, as well as etiology of meningitis and time of CSF or blood specimens' collection. This study provides an overview of different immunologic biomarkers as diagnostic markers for the identification of bacterial meningitis and their efficiencies in the differentiating of bacterial from viral meningitis.
Topics: Humans; Meningitis, Bacterial; Biomarkers; Meningitis, Viral; Inflammation; Cytokines; Bacteria
PubMed: 37419301
DOI: 10.1016/j.cca.2023.117470 -
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 -
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 the Neurological Sciences Apr 2020Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges (pia, subarachnoid space and arachnoid mater), and dura.... (Review)
Review
Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges (pia, subarachnoid space and arachnoid mater), and dura. Leptomeningeal metastases (LM), also known by different terms including neoplastic meningitis and carcinomatous meningitis, occur in both solid tumors and hematologic malignancies. This review will focus exclusively on LM arising from solid tumors with a goal of providing the reader an understanding of the epidemiology, pathophysiology, clinical presentation, prognostication, current management and future directions.
Topics: Arachnoid; Dura Mater; Humans; Meningeal Carcinomatosis; Meningeal Neoplasms; Meninges; Meningitis, Bacterial; Neoplasms
PubMed: 32007755
DOI: 10.1016/j.jns.2020.116706 -
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 -
Current Opinion in Infectious Diseases Jun 2020Central nervous system (CNS) infections associated with HIV remain significant contributors to morbidity and mortality, particularly among people living with HIV (PLWH)... (Review)
Review
PURPOSE OF REVIEW
Central nervous system (CNS) infections associated with HIV remain significant contributors to morbidity and mortality, particularly among people living with HIV (PLWH) in resource-limited settings worldwide. In this review, we discuss several recent important scientific discoveries in the prevention, diagnosis, and management around two of the major causes of CNS opportunistic infections-tuberculous meningitis (TBM) and cryptococcal meningitis including immune reconstitution syndrome (IRIS) associated with cryptococcal meningitis. We also discuss the CNS as a possible viral reservoir, highlighting Cerebrospinal fluid viral escape.
RECENT FINDINGS
CNS infections in HIV-positive people in sub-Saharan Africa contribute to 15-25% of AIDS-related deaths. Morbidity and mortality in those is associated with delays in HIV diagnosis, lack of availability for antimicrobial treatment, and risk of CNS IRIS. The CNS may serve as a reservoir for replication, though it is unclear whether this can impact peripheral immunosuppression.
SUMMARY
Significant diagnostic and treatment advances for TBM and cryptococcal meningitis have yet to impact overall morbidity and mortality according to recent data. Lack of early diagnosis and treatment initiation, and also maintenance on combined antiretroviral treatment are the main drivers of the ongoing burden of CNS opportunistic infections. The CNS as a viral reservoir has major potential implications for HIV eradication strategies, and also control of CNS opportunistic infections.
Topics: Central Nervous System Infections; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Meningitis, Cryptococcal; Opportunistic Infections; Tuberculosis, Meningeal; Viruses
PubMed: 32332225
DOI: 10.1097/QCO.0000000000000652 -
Progress in Brain Research 2024The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical... (Review)
Review
The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical findings and meningeal damage. Galen proposed that the dura was attached only at the sutures, and he was the first to describe the pia in humans. In the Middle Ages, new interest in the management of meningeal injuries arose, with renewed interest in relating clinical changes to intracranial injuries. These associations were neither consistent nor accurate. The Renaissance brought little change. It was in the 18th century that it became clear that the indication for opening the cranium following trauma was to relieve pressure from hematomas. Moreover, the important clinical findings on which to base an indication for intervention were changes in the level of consciousness.
Topics: Humans; Meninges; History, Ancient; History, 19th Century; History, 18th Century; History, 17th Century; History, Medieval; History, 16th Century; History, 15th Century; History, 20th Century
PubMed: 38705713
DOI: 10.1016/bs.pbr.2024.02.020