-
Journal of Neuroinflammation May 2023The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an... (Review)
Review
The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an immunologically active site. Meningeal immunity has emerged as a key factor in modulating proper brain function and social behavior, performing constant immune surveillance of the CNS, and participating in several neurological diseases. However, it remains to be determined how meningeal immunity contributes to CNS physiology and pathophysiology. With the advances in single-cell omics, new approaches, such as single-cell technologies, unveiled the details of cellular and molecular mechanisms underlying meningeal immunity in CNS homeostasis and dysfunction. These new findings contradict some previous dogmas and shed new light on new possible therapeutic targets. In this review, we focus on the complicated multi-components, powerful meningeal immunosurveillance capability, and its crucial involvement in physiological and neuropathological conditions, as recently revealed by single-cell technologies.
Topics: Humans; Meninges; Central Nervous System; Nervous System Diseases
PubMed: 37231449
DOI: 10.1186/s12974-023-02803-z -
Journal of Veterinary Diagnostic... Sep 2022Meningioangiomatosis (MA) is a rare proliferative meningovascular entity that has been described mainly in humans and dogs. Here we describe MA in a 13-y-old spayed...
Meningioangiomatosis (MA) is a rare proliferative meningovascular entity that has been described mainly in humans and dogs. Here we describe MA in a 13-y-old spayed female domestic shorthaired cat that died 5 d after acute change in behavior, open-mouth breathing, seizures, hyperthermia, and inability to walk. On MRI, the lesion appeared predominantly as extraparenchymal hemorrhage. Autopsy changes consisted of a dark-red, hemorrhagic plaque that expanded the leptomeninges and outer neuroparenchyma of the right piriform and temporal telencephalic lobes, chalky white nodules in the peripancreatic fat, and yellow fluid in the abdomen. Histologically, the lesion in the brain consisted of leptomeningeal thickening by spindle cells that effaced the subarachnoid spaces and extended perivascularly into the underlying cerebral cortex. Spindle cells were arranged as streams or whorls around blood vessels, and had slender eosinophilic cytoplasm and elongated nuclei with coarsely stippled chromatin and 1 or 2 distinct nucleoli. There was extensive hemorrhage, clusters of hemosiderin-laden macrophages, and mineralization throughout. Spindle cells had positive immunolabeling for vimentin. A striking MRI and gross feature in our case was the extensive hemorrhage associated with the MA lesion. Additional findings included suppurative pancreatitis with peritonitis and supraspinatus myonecrosis.
Topics: Animals; Autopsy; Brain; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meninges; Meningioma; Seizures
PubMed: 35833693
DOI: 10.1177/10406387221110912 -
The Lancet. Infectious Diseases Sep 2019
Topics: Adult; Botswana; Cohort Studies; Cryptococcus; Humans; Meningitis; Meningitis, Cryptococcal
PubMed: 31478513
DOI: 10.1016/S1473-3099(19)30442-6 -
Fluids and Barriers of the CNS Dec 2023Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the...
Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the brain is based on postmortem macroscopic examination. Ultrastructural and single cell transcriptome analyses have documented that the 3 meningeal layers can be subdivided into several distinct layers based on cellular characteristics. We here re-examined the existence of a 4 meningeal membrane, Subarachnoid Lymphatic-like Membrane or SLYM in Prox1-eGFP reporter mice. Imaging of freshly resected whole brains showed that SLYM covers the entire brain and brain stem and forms a roof shielding the subarachnoid cerebrospinal fluid (CSF)-filled cisterns and the pia-adjacent vasculature. Thus, SLYM is strategically positioned to facilitate periarterial influx of freshly produced CSF and thereby support unidirectional glymphatic CSF transport. Histological analysis showed that, in spinal cord and parts of dorsal cortex, SLYM fused with the arachnoid barrier layer, while in the basal brain stem typically formed a 1-3 cell layered membrane subdividing the subarachnoid space into two compartments. However, great care should be taken when interpreting the organization of the delicate leptomeningeal membranes in tissue sections. We show that hyperosmotic fixatives dehydrate the tissue with the risk of shrinkage and dislocation of these fragile membranes in postmortem preparations.
Topics: Mice; Animals; Meninges; Dura Mater; Arachnoid; Subarachnoid Space; Cerebral Cortex
PubMed: 38098084
DOI: 10.1186/s12987-023-00500-w -
The Journal of Experimental Medicine Aug 2022A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et...
A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220035) employ light sheet fluorescence imaging of intact mouse heads to provide a more comprehensive chart of the meningeal lymphatic vasculature and draw a parallel between lymphatic drainage of cerebrospinal fluid in mice and humans.
Topics: Animals; Brain; Lymphatic System; Lymphatic Vessels; Mammals; Meninges; Mice; Spinal Cord
PubMed: 35789368
DOI: 10.1084/jem.20220891 -
BMC Veterinary Research May 2021Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation mainly in retropharyngeal, tracheobronchial, mediastinal lymph nodes and lungs of...
BACKGROUND
Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation mainly in retropharyngeal, tracheobronchial, mediastinal lymph nodes and lungs of bovines. The presence of these lesions in other tissues such as the eyeball is very rare and difficult to diagnose. This study describes macroscopic and microscopic pathological findings in a calf with ocular and meningeal tuberculosis.
CASE PRESENTATION
March 2019, an eight-month-old Holstein Friesian calf was identified in a dairy farm located in central Mexico with a clinical cough, anorexia, incoordination, corneal opacity and vision loss. At necropsy, pneumonia, lymphadenitis, meningitis, and granulomatous iridocyclitis were observed. The histopathological examination revealed granulomatous lesions in lung tissue, lymph nodes, meninges and eyes with the presence of acid-fast bacilli associated with Mycobacterium spp.
CONCLUSION
To the best of our knowledge, this is the first report that describes macroscopic and microscopic pathological findings of ocular tuberculosis in cattle. This report highlights the importance of considering bovine tuberculosis in the differential diagnosis of corneal opacity and loss of vision in cattle.
Topics: Animals; Cattle; Eye Diseases; Granuloma; Meningitis; Mexico; Mycobacterium; Tuberculosis, Bovine; Tuberculosis, Ocular
PubMed: 33964902
DOI: 10.1186/s12917-021-02893-y -
Fluids and Barriers of the CNS Feb 2023The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic...
BACKGROUND
The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal fluid-filled subarachnoid space and across the brain parenchyma via their connection to glymphatic structures. Meningeal fibroblasts lining and traversing the subarachnoid space have direct impact on the composition of the cerebrospinal fluid through endocytotic uptake as well as extensive protein secretion. In addition, the meninges are an active site for immunological processes and act as gatekeeper for immune cells entering the brain. During aging in mice, lymphatic drainage from the brain is less efficient contributing to neurodegenerative processes. Aging also affects the immunological status of the meninges, with increasing numbers of T cells, changing B cell make-up, and altered macrophage complement.
METHODS
We employed RNASeq to measure gene expression and to identify differentially expressed genes in meninges isolated from young and aged mice. Using Ingenuity pathway, GO term, and MeSH analyses, we identified regulatory pathways and cellular functions in meninges affected by aging.
RESULTS
Aging had profound impact on meningeal gene expression. Pathways related to innate as well as adaptive immunity were affected. We found evidence for increasing numbers of T and B lymphocytes and altered activity profiles for macrophages and other myeloid cells. Furthermore, expression of pro-inflammatory cytokine and chemokine genes increased with aging. Similarly, the complement system seemed to be more active in meninges of aged mice. Altered expression of solute carrier genes pointed to age-dependent changes in cerebrospinal fluid composition. In addition, gene expression for secreted proteins showed age-dependent changes, in particular, genes related to extracellular matrix composition and organization were affected.
CONCLUSIONS
Aging has profound effects on meningeal gene expression; thereby affecting the multifaceted functions meninges perform to maintain the homeostasis of the central nervous system. Thus, age-dependent neurodegenerative processes and cognitive decline are potentially in part driven by altered meningeal function.
Topics: Mice; Animals; Meninges; Central Nervous System; Brain; Aging; Gene Expression
PubMed: 36747230
DOI: 10.1186/s12987-023-00412-9 -
Stroke Jun 2023
Topics: Humans; Lymphatic System; Stroke; Meninges; Neutrophils; Brain Ischemia
PubMed: 37216448
DOI: 10.1161/STROKEAHA.123.043424 -
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 -
Acta Neurochirurgica Jun 2024The discovery of the glymphatic system has fundamentally altered our comprehension of cerebrospinal fluid transport and the removal of waste from brain metabolism. In... (Review)
Review
The discovery of the glymphatic system has fundamentally altered our comprehension of cerebrospinal fluid transport and the removal of waste from brain metabolism. In the past decade, since its initial characterization, research on the glymphatic system has surged exponentially. Its potential implications for central nervous system disorders have sparked significant interest in the field of neurosurgery. Nonetheless, ongoing discussions and debates persist regarding the concept of the glymphatic system, and our current understanding largely relies on findings from experimental animal studies. This review aims to address several key inquiries: What methodologies exist for evaluating glymphatic function in humans today? What is the current evidence supporting the existence of a human glymphatic system? Can the glymphatic system be considered distinct from the meningeal-lymphatic system? What is the human evidence for glymphatic-meningeal lymphatic system failure in neurosurgical diseases? Existing literature indicates a paucity of techniques available for assessing glymphatic function in humans. Thus far, intrathecal contrast-enhanced magnetic resonance imaging (MRI) has shown the most promising results and have provided evidence for the presence of a glymphatic system in humans, albeit with limitations. It is, however, essential to recognize the interconnection between the glymphatic and meningeal lymphatic systems, as they operate in tandem. There are some human studies demonstrating deteriorations in glymphatic function associated with neurosurgical disorders, enriching our understanding of their pathophysiology. However, the translation of this knowledge into clinical practice is hindered by the constraints of current glymphatic imaging modalities.
Topics: Humans; Glymphatic System; Neurosurgical Procedures; Meninges; Animals; Magnetic Resonance Imaging
PubMed: 38904802
DOI: 10.1007/s00701-024-06161-4