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Science (New York, N.Y.) Jan 2023The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that...
The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.
Topics: Animals; Humans; Mice; Dura Mater; Endothelium; Subarachnoid Space; Epithelium; Brain; Cerebrospinal Fluid
PubMed: 36603070
DOI: 10.1126/science.adc8810 -
Current Opinion in Infectious Diseases Jun 2022Neurocysticercosis (NCC) is an important cause of neurological disease worldwide, including imported cases in nonendemic countries. (Review)
Review
UNLABELLED
Neurocysticercosis (NCC) is an important cause of neurological disease worldwide, including imported cases in nonendemic countries.
PURPOSE OF REVIEW
The purpose of this review is to update information on diagnosis, management, and prevention of neurocysticercosis.
RECENT FINDINGS
WHO and Infectious Diseases Society of America/American Society of Tropical Medicine and Hygiene guidelines emphasize the importance of corticosteroids and antiparasitic drugs for viable parenchymal disease and single enhancing lesions. Subarachnoid NCC is associated with a high fatality rate unless optimally treated. Advances in subarachnoid NCC include use of prolonged antiparasitic and anti-inflammatory courses and the increasing use of antigen-detection and quantitative PCR assays in diagnosis and follow-up. Emerging data support the safety and efficacy of minimally invasive surgery in ventricular cases. Calcified neurocysticercosis continues to be associated with a high burden of disease. Field studies are demonstrating the feasibility of eradication using a combination of mass chemotherapy for human tapeworms and vaccination/treatment of porcine cysticercosis.
SUMMARY
NCC remains an important and challenging cause of neurological disease with significant morbidity despite advances in treatment and prevention.
Topics: Animals; Anti-Inflammatory Agents; Antiparasitic Agents; Humans; Hygiene; Neurocysticercosis; Subarachnoid Space; Swine
PubMed: 35665719
DOI: 10.1097/QCO.0000000000000831 -
The New England Journal of Medicine Dec 2021
Review
Topics: Brain; Cerebrospinal Fluid Leak; Headache; Humans; Intracranial Hypotension; Magnetic Resonance Imaging; Myelography; Optic Nerve; Subarachnoid Space
PubMed: 34874632
DOI: 10.1056/NEJMra2101561 -
Nature Communications Sep 2020The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid...
The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.
Topics: Animals; Aquaporin 4; Astrocytes; Brain; Cerebrospinal Fluid; Circadian Rhythm; Cisterna Magna; Glymphatic System; Lymph Nodes; Mice
PubMed: 32879313
DOI: 10.1038/s41467-020-18115-2 -
Neuron Dec 2023Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal...
Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
Topics: Mice; Animals; Meninges; Arachnoid; Pia Mater; Choroid Plexus; Brain
PubMed: 37776854
DOI: 10.1016/j.neuron.2023.09.002 -
Neurologia Medico-chirurgica Feb 2021Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure...
Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
Topics: Aged; Aged, 80 and over; Biomarkers; Cerebral Ventricles; Cerebrospinal Fluid Pressure; Cerebrospinal Fluid Shunts; Cerebrovascular Circulation; Cognitive Dysfunction; Dementia; Female; Gait Disorders, Neurologic; Humans; Hydrocephalus, Normal Pressure; Japan; Magnetic Resonance Imaging; Male; Neuroimaging; Neurologic Examination; Neuropsychological Tests; Nuclear Medicine; Prognosis; Subarachnoid Space; Urinary Incontinence
PubMed: 33455998
DOI: 10.2176/nmc.st.2020-0292 -
The Journal of Experimental Medicine Feb 2023Arachnoid granulations (AG) are poorly investigated. Historical reports suggest that they regulate brain volume by passively transporting cerebrospinal fluid (CSF) into...
Arachnoid granulations (AG) are poorly investigated. Historical reports suggest that they regulate brain volume by passively transporting cerebrospinal fluid (CSF) into dural venous sinuses. Here, we studied the microstructure of cerebral AG in humans with the aim of understanding their roles in physiology. We discovered marked variations in AG size, lobation, location, content, and degree of surface encapsulation. High-resolution microscopy shows that AG consist of outer capsule and inner stromal core regions. The fine and porous framework suggests uncharacterized functions of AG in mechanical CSF filtration. Moreover, internal cytokine and immune cell enrichment imply unexplored neuroimmune properties of these structures that localize to the brain-meningeal lymphatic interface. Dramatic age-associated changes in AG structure are additionally identified. This study depicts for the first time microscopic networks of internal channels that communicate with perisinus spaces, suggesting that AG subserve important functions as transarachnoidal flow passageways. These data raise new theories regarding glymphatic-lymphatic coupling and mechanisms of CSF antigen clearance, homeostasis, and diseases.
Topics: Humans; Bone Marrow; Arachnoid; Dura Mater; Lymphatic System; Lymphatic Vessels
PubMed: 36469302
DOI: 10.1084/jem.20220618 -
Nature Mar 2024The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between...
The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.
Topics: Animals; Humans; Mice; Arachnoid; Biological Transport; Brain; Dura Mater; Encephalomyelitis, Autoimmune, Experimental; Gene Expression Profiling; Magnetic Resonance Imaging; Mice, Transgenic; Subarachnoid Space; Cerebrospinal Fluid; Veins
PubMed: 38326613
DOI: 10.1038/s41586-023-06993-7 -
Acta Neurochirurgica Jan 2021
Topics: Arachnoid; Arachnoiditis; Arnold-Chiari Malformation; Humans; Syringomyelia
PubMed: 32948891
DOI: 10.1007/s00701-020-04584-3