Conserved meningeal lymphatic drainage circuits in mice and humans
Laurent JacobJosé M. BritoStéphanie LenckCéline CorcyFarhat BenbelkacemLuiz Henrique GeraldoYunling XuJean-Mickael ThomasMarie-Rénée El KamouhMyriam SpajerMarie‐Claude PotierStéphane Haı̈kMichel KalamaridesBruno StankoffStéphane LehéricyAnne EichmannJean‐Léon Thomas
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Abstract:
Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations after OVA-A555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel-wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies. We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extended anterior MLV network around the cavernous sinus, with exit routes through the foramina of emissary veins. VW-MRI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.Keywords:
Dural venous sinuses
Glymphatic System
Meninges
Pia mater
Meninges
Pia mater
Subarachnoid space
Middle meningeal artery
Subdural space
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Ultrastruct of the dog arachnoid membrane, pia (vascular) mater, internal layer of the dura mater, human arachnoid membrane, subarachnoid alveolar walls and canals transporting liquor into the subarachnoid space have been studied. From the literature analysed and from his own data the author considers the system of the meninges and intermeningeal spaces as a system of extracerebral barriers devided into 3 stdructural-functional groups: 1--barriers dealing with liquor outflow from the subarachnoid space into the blood stream (lgb-I lgb-II); 2--barriers dealing with metabolic processes between the liquor and the borderline tissues (lcb, lmb, lnb, etc.); 3--histo-haematic barriers between blood and tissue elements of the pia mater, dura mater and paravasal nerve trunks of the brain magistral arteries. Morphological substrates of some extracerebral barriers are described at a submicroscopical level.
Meninges
Subarachnoid space
Pia mater
Perivascular space
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Previous studies of samples from cranial meninges have created doubts about the existence of a virtual subdural space. We examined the ultrastructure of spinal meninges from three human cadavers immediately after death to see whether there is a virtual subdural space at this level. The arachnoid mater had two portions: a compact laminar portion covering the dural sac internal surface and a trabecular portion extending like a spider web around the pia mater. There was a cellular interface between the laminar arachnoid and the internal layer of the dura that we called the dura-arachnoid interface. There was no subdural space in those specimens where the dura mater was macroscopically in continuity with the arachnoid trabecules. In the specimens where the dura mater was separated from the arachnoid, we found fissures in between the neurothelial cells that extended throughout the interface. We hypothesize that the subdural space would have its origin within the dura-arachnoid interface when the neurothelial cells break up, creating in this way a real subdural space.
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The spinal cord and brain are encased within three layers of tissue called the meninges. The spinal meninges specifically enclose the spinal cord and stretch from the brainstem down to the filum terminale. The layers of the meninges are, from deep to superficial, the pia mater, the arachnoid mater, and the dura mater. The names of these layers give information on their qualities. Pia, which is Latin for “loving” and mater, which is Latin for “mother,” make up the pia mater, or “loving mother,” which is directly attached to the spinal cord and inseparable. The arachnoid mater contains a web of fiber beneath it in the subarachnoid space, and the dura mater or “hard mother” is the tough outer layer of the meninges. The principal function of the spinal meninges is to protect and support the spinal cord.
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Viral, bacterial and fungal infections are the most common causes of meningitis. However, subarachnoid haemorrhage, chemicals, cancers and certain noninfectious inflammatory conditions may also lead to meningitis.
In this article we discuss bacterial meningitis, with specific emphasis on the most common causes of bacterial meningitis occurring after the neonatal period, namely Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.
The brain and spinal cord are covered by membranes called the meninges. The meninges are made up of three separate membranes namely the dura mater, the arachnoid and the pia mater. The dura mater is situated directly beneath and adherent to the skull. The pia mater is the membrane that covers the brain and the arachnoid is located between the dura mater and the pia mater. The region between the arachnoid and the pia mater is where the cerebrospinal fluid (CSF) passes and is called the subarachnoid space. Meningitis is an inflammatory disease of the pia mater and the arachnoid membranes including the CSF in the subarachnoid space and in the cerebral ventricles.
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Infiltration (HVAC)
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Abstract In infectious meningitis, pathogens preferentially attack the leptomeninges (pia mater and arachnoid) rather than the pachymeninges (dura mater). This study aims to provide ultra‐anatomical insights from our extensive collection of electron microscopy images and propose mechanisms, highlighting structures that favor the introduction, adherence, colonization, and proliferation of microorganisms leading to spinal meningitis. Over several years, we analyzed an extensive collection of transmission and scanning electron microscopy images of human spinal meninges captured in our laboratories. Upon examining 378 of those images, we identified potential sites for the iatrogenic or hematogenic introduction and adherence of microorganisms, as well as sites for their colonization and proliferation. These included the outer surface of the spinal dural sac, structures within the epidural space, and the spinal dural sac itself, which comprises compact dura mater with interwoven collagen fibers and tightly bound arachnoid cells. Also, the subdural (extra‐arachnoid) compartment, consisting of fragile neurothelial cells prone to rupture under force, formed an acquired spinal subdural space, a new subarachnoid compartment, limited by arachnoid trabeculae, that surrounded the nerve roots and spinal cord and the pia mater. Macrophages, fibroblasts, mast cells, and plasma cells were also observed within the dura mater, arachnoid layer, arachnoid trabeculae, and pia mater. These images illustrate how the characteristics of the meningeal layers could contribute to bacterial adhesion and proliferation at various locations, inducing selective inflammation during (iatrogenic) spinal meningitis. In addition, the images help to explain why magnetic resonance imaging enhancement appears preferentially at specific sites.
Leptomeninges
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Subdural space
Perivascular space
Epidural space
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Alma mater
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Falx cerebri
Tentorium cerebelli
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Little information exists about which spinal meninx is the principal permeability barrier between the epidural space and the spinal cord or about what physicochemical properties of drug molecules govern their meningeal permeability. To better understand these aspects of epidural pharmacokinetics, the authors measured the permeability of morphine and alfentanil through the different components of the spinal meninges-dura mater, arachnoid mater, and pia mater-of dogs and monkeys in vitro. Live meningeal tissue from either species (dura mater alone, pia mater alone, or intact dura-arachnoid-pia) was placed between two fluid reservoirs of a temperature-controlled diffusion cell. The permeability of the tissues to each opioid was determined by placing the opioid in one of the reservoirs of the diffusion cell and measuring the rate at which the drug diffused through the tissue and appeared in the second reservoir. The arachnoid mater was found to be the major meningeal diffusion barrier between the epidural space and the spinal cord. Alfentanil was 3.7 times more permeable than morphine through all three meninges, suggesting that increased lipid solubility increases meningeal permeability. However, neither lipid solubility nor molecular weight adequately explained the difference in permeability between morphine and alfentanil. The authors conclude that this in vitro model has significant utility for studies aimed at predicting in vivo meningeal permeability and hence the potency and rapidity of action of any opioid administered by the epidural route.
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Pia mater
Epidural space
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Extravasation
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