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Genesis (New York, N.Y. : 2000) May 2019The meninges are membranous layers surrounding the central nervous system. In the head, the meninges lie between the brain and the skull, and interact closely with both... (Review)
Review
The meninges are membranous layers surrounding the central nervous system. In the head, the meninges lie between the brain and the skull, and interact closely with both during development. The cranial meninges originate from a mesenchymal sheath on the surface of the developing brain, called primary meninx, and undergo differentiation into three layers with distinct histological characteristics: the dura mater, the arachnoid mater, and the pia mater. While genetic regulation of meningeal development is still poorly understood, mouse mutants and other models with meningeal defects have demonstrated the importance of the meninges to normal development of the calvaria and the brain. For the calvaria, the interactions with the meninges are necessary for the progression of calvarial osteogenesis during early development. In later stages, the meninges control the patterning of the skull and the fate of the sutures. For the brain, the meninges regulate diverse processes including cell survival, cell migration, generation of neurons from progenitors, and vascularization. Also, the meninges serve as a stem cell niche for the brain in the postnatal life. Given these important roles of the meninges, further investigation into the molecular mechanisms underlying meningeal development can provide novel insights into the coordinated development of the head.
Topics: Animals; Arachnoid; Brain; Cell Differentiation; Developmental Biology; Dura Mater; Humans; Meninges; Pia Mater; Skull
PubMed: 30801905
DOI: 10.1002/dvg.23288 -
Cell Feb 2021Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However,...
Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Antigens; Cellular Senescence; Chemokine CXCL12; Cranial Sinuses; Dura Mater; Female; Homeostasis; Humans; Immunity; Male; Mice, Inbred C57BL; Phenotype; Stromal Cells; T-Lymphocytes; Mice
PubMed: 33508229
DOI: 10.1016/j.cell.2020.12.040 -
Arquivos de Neuro-psiquiatria Dec 2020Hypertrophic pachymeningitis (HP) is a non-usual manifestation of rheumatologic, infectious, and neoplastic diseases. Etiological diagnosis is a challenge, but when made...
IMPORTANCE
Hypertrophic pachymeningitis (HP) is a non-usual manifestation of rheumatologic, infectious, and neoplastic diseases. Etiological diagnosis is a challenge, but when made promptly it creates a window of opportunity for treatment, with the possibility of a total reversal of symptoms.
OBSERVATIONS
HP is an inflammatory process of the dura mater that can occur as a manifestation of sarcoidosis, granulomatosis with polyangiitis, and IgG4-related disease. The HP case evaluation is extensive and includes central nervous system imaging, cerebrospinal fluid analysis, serology, rheumatologic tests, and systemic survey for other manifestations sites. After systemic investigation, meningeal biopsy might be necessary. Etiology guides HP treatment, and autoimmune disorders are treated with corticosteroids alone or associated with an immunosuppressor.
CONCLUSION
HP is a manifestation of several diseases, and a precise etiological diagnosis is crucial because of the difference among treatments. An extensive investigation of patients with HP helps early diagnosis and correct treatment.
Topics: Adrenal Cortex Hormones; Dura Mater; Humans; Hypertrophy; Magnetic Resonance Imaging; Meningitis
PubMed: 33295420
DOI: 10.1590/0004-282X20200073 -
Science (New York, N.Y.) Jul 2021The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here,...
The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the mouse meninges contain a pool of monocytes and neutrophils supplied not from the blood but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation, CNS-infiltrating myeloid cells can originate from brain borders and display transcriptional signatures distinct from their blood-derived counterparts. Thus, CNS borders are populated by myeloid cells from adjacent bone marrow niches, strategically placed to supply innate immune cells under homeostatic and pathological conditions. These findings call for a reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches that harness meningeal immune cells.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Brain; Cell Movement; Central Nervous System; Central Nervous System Diseases; Dura Mater; Encephalomyelitis, Autoimmune, Experimental; Homeostasis; Meninges; Mice; Monocytes; Myeloid Cells; Neutrophils; Skull; Spinal Cord; Spinal Cord Injuries; Spine
PubMed: 34083447
DOI: 10.1126/science.abf7844 -
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 -
The Journal of Clinical Investigation Sep 2017Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we... (Review)
Review
Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Central Nervous System; Central Nervous System Diseases; Dura Mater; Extracellular Fluid; Humans; Immune System; Lymph Nodes; Lymphatic System; Lymphatic Vessels; Meninges; Neuroglia
PubMed: 28862640
DOI: 10.1172/JCI90603 -
Science (New York, N.Y.) Jul 2021The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These cells are thought to derive from the systemic...
The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis. B cells reach the meninges from the calvaria through specialized vascular connections. This calvarial-meningeal path of B cell development may provide the CNS with a constant supply of B cells educated by CNS antigens. Conversely, we show that a subset of antigen-experienced B cells that populate the meninges in aging mice are blood-borne. These results identify a private source for meningeal B cells, which may help maintain immune privilege within the CNS.
Topics: Aging; Animals; B-Lymphocyte Subsets; B-Lymphocytes; Bone Marrow Cells; Cell Movement; Central Nervous System; Dura Mater; Fibroblasts; Homeostasis; Immune Privilege; Lymphopoiesis; Meninges; Mice; Plasma Cells; Single-Cell Analysis; Skull
PubMed: 34083450
DOI: 10.1126/science.abf9277 -
Clinical Interventions in Aging 2019Lumbar disc herniation into the dural space is a very rare phenomenon of degenerative lumbar lesions in the elderly population, and its potential pathogenesis and... (Review)
Review
BACKGROUND
Lumbar disc herniation into the dural space is a very rare phenomenon of degenerative lumbar lesions in the elderly population, and its potential pathogenesis and natural course remain unclear.
CASE DESCRIPTION
We describe a rare case of intradural lumbar disc herniation. A 68-year-old man presented with progressive lower back pain and radiating pain and numbness in both legs for 3 years. Magnetic resonance imaging revealed a large herniated disc at L4-L5. Posterior discectomy and fusion of the L4-L5 was performed after conservative treatment failed. Intraoperatively, only minimal disc fragments in the epidural space were found after meticulous probing following laminectomy of the L4-L5 vertebrae. The dorsal dura mater was saturated, tense, and bulged at the L4-L5 levels; additionally, an intradural mass was palpable and confirmed by intraoperative ultrasonography. Subsequently, dorsal middle durotomy was performed. Upon opening the dural sac, a large cauliflower-like mass similar to nucleus pulposus tissue was found near the arachnoid membrane. The mass was dissociative and could be completely resected. The dorsal dural incisions were closed after careful exploration, followed by fixation and fusion of the L4-L5 levels. Pathological examination revealed disc tissue with central balloon-type cystic degenerative changes. The patient's lower back pain and radiating pain and numbness of both legs improved remarkably postoperatively, and he became asymptomatic at 3 months postoperatively.
CONCLUSION
Intradural lumbar disc herniation should be highly suspected when intraoperative findings are incompatible with findings from the preoperative imaging examination, and it could be further confirmed via intraoperative ultrasonography and pathological examination of the resected tissue from the dural space. Prompt surgery is recommended, and surgical results are usually favorable. We also reviewed the literature and discussed the potential pathogenesis, natural course, diagnosis, and treatment of intradural lumbar disc herniation.
Topics: Aged; Dura Mater; Humans; Intervertebral Disc Displacement; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Radiculopathy
PubMed: 31920293
DOI: 10.2147/CIA.S228717 -
Cell Jan 2021Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in...
Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1 mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.
Topics: Animals; Behavior, Animal; Cognition; Cranial Sutures; Craniosynostoses; Dura Mater; Gelatin; Gene Expression Profiling; Hand Strength; Intracranial Pressure; Locomotion; Mesenchymal Stem Cells; Methacrylates; Mice, Inbred C57BL; Motor Activity; Organ Size; Regeneration; Skull; Twist-Related Protein 1; Wnt Signaling Pathway; Mice
PubMed: 33417861
DOI: 10.1016/j.cell.2020.11.037 -
JAMA Neurology May 2019Various signs may be observed on brain magnetic resonance imaging (MRI) in patients with spontaneous intracranial hypotension (SIH). However, the lack of a...
IMPORTANCE
Various signs may be observed on brain magnetic resonance imaging (MRI) in patients with spontaneous intracranial hypotension (SIH). However, the lack of a classification system integrating these findings limits decision making in clinical practice.
OBJECTIVE
To develop a probability score based on the most relevant brain MRI findings to assess the likelihood of an underlying spinal cerebrospinal fluid (CSF) leak in patients with SIH.
DESIGN, SETTING, AND PARTICIPANTS
This case-control study in consecutive patients investigated for SIH was conducted at a single hospital department from February 2013 to October 2017. Patients with missing brain MRI data were excluded. Three blinded readers retrospectively reviewed the brain MRI scans of patients with SIH and a spinal CSF leak, patients with orthostatic headache without a CSF leak, and healthy control participants, evaluating 9 quantitative and 7 qualitative signs. A predictive diagnostic score based on multivariable backward logistic regression analysis was then derived. Its performance was validated internally in a prospective cohort of patients who had clinical suspicion for SIH.
MAIN OUTCOMES AND MEASURES
Likelihood of a spinal CSF leak based on the proposed diagnostic score.
RESULTS
A total of 152 participants (101 female [66.4%]; mean [SD] age, 46.1 [14.3] years) were studied. These included 56 with SIH and a spinal CSF leak, 16 with orthostatic headache without a CSF leak, 60 control participants, and 20 patients in the validation cohort. Six imaging findings were included in the final scoring system. Three were weighted as major (2 points each): pachymeningeal enhancement, engorgement of venous sinus, and effacement of the suprasellar cistern of 4.0 mm or less. Three were considered minor (1 point each): subdural fluid collection, effacement of the prepontine cistern of 5.0 mm or less, and mamillopontine distance of 6.5 mm or less. Patients were classified into groups at low, intermediate, or high probability of having a spinal CSF leak, with total scores of 2 points or fewer, 3 to 4 points, and 5 points or more, respectively, on a scale of 9 points. The discriminatory ability of the proposed score could be demonstrated in the validation cohort.
CONCLUSIONS AND RELEVANCE
This 3-tier predictive scoring system is based on the 6 most relevant brain MRI findings and allows assessment of the likelihood (low, intermediate, or high) of a positive spinal imaging result in patients with SIH. It may be useful in identifying patients with SIH who are leak positive and in whom further invasive myelographic examinations are warranted before considering targeted therapy.
Topics: Adolescent; Adult; Aged; Brain; Case-Control Studies; Cerebrospinal Fluid Leak; Cranial Sinuses; Dura Mater; Female; Humans; Intracranial Hypotension; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Myelography; Subdural Space; Tomography, X-Ray Computed; Young Adult
PubMed: 30776059
DOI: 10.1001/jamaneurol.2018.4921