A mesothelium divides the subarachnoid space into functional compartments

Møllgård, Kjeld; Beinlich, Felix; Kusk, Peter; Miyakoshi, Leo M; Delle, Christine; Plá, Virginia; Hauglund, Natalie L.; Esmail, Tina; Rasmussen, Martin Kaag; Gomolka, Ryszard; Mori, Yutaka; Nedergaard, Maiken

doi:10.1126/science.adc8810

Cited by 130 publications

(173 citation statements)

References 52 publications

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“…Second, gadobutrol is a hydrophilic substance that does not pass the intact BBB, nor does it permeate the cell membrane or interact with other molecules of the brain. Third, the transport of plasma biomarkers and CSF tracer in the subarachnoid compartments may differ due to the membranes compartmentalizing the subarachnoid space 44 , 45 . In this regard, ref.…”

Section: Discussionmentioning

confidence: 99%

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Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

et al. 2023

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Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-β (Aβ40 and Aβ42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.

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Section: Discussionmentioning

confidence: 99%

“…In this regard, ref. 45 recently described a subarachnoid lymphatic-like membrane (SLYM) compartmentalizing the subarachnoid space, where this mesothelial membrane was impermeable to substances >3 kDa.…”

Section: Discussionmentioning

confidence: 99%

Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

et al. 2023

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“…Recently, Møllgård et al found the presence of a fourth cranial meningeal layer in the mouse brain, naming it subarachnoid lymphatic-like membrane (SLYM) [ 38 ]. We did not detect such a fourth layer in the human ON specimen investigated here.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Large-scale morphometry of the subarachnoid space of the optic nerve

Rossinelli

Killer

Meyer

et al. 2023

Fluids Barriers CNS

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Background The meninges, formed by dura, arachnoid and pia mater, cover the central nervous system and provide important barrier functions. Located between arachnoid and pia mater, the cerebrospinal fluid (CSF)-filled subarachnoid space (SAS) features a variety of trabeculae, septae and pillars. Like the arachnoid and the pia mater, these structures are covered with leptomeningeal or meningothelial cells (MECs) that form a barrier between CSF and the parenchyma of the optic nerve (ON). MECs contribute to the CSF proteome through extensive protein secretion. In vitro, they were shown to phagocytose potentially toxic proteins, such as α-synuclein and amyloid beta, as well as apoptotic cell bodies. They therefore may contribute to CSF homeostasis in the SAS as a functional exchange surface. Determining the total area of the SAS covered by these cells that are in direct contact with CSF is thus important for estimating their potential contribution to CSF homeostasis. Methods Using synchrotron radiation-based micro-computed tomography (SRµCT), two 0.75 mm-thick sections of a human optic nerve were acquired at a resolution of 0.325 µm/pixel, producing images of multiple terabytes capturing the geometrical details of the CSF space. Special-purpose supercomputing techniques were employed to obtain a pixel-accurate morphometric description of the trabeculae and estimate internal volume and surface area of the ON SAS. Results In the bulbar segment, the ON SAS microstructure is shown to amplify the MECs surface area up to 4.85-fold compared to an “empty” ON SAS, while just occupying 35% of the volume. In the intraorbital segment, the microstructure occupies 35% of the volume and amplifies the ON SAS area 3.24-fold. Conclusions We provided for the first time an estimation of the interface area between CSF and MECs. This area is of importance for estimating a potential contribution of MECs on CSF homeostasis.

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“…SLIM has a structure similar to the mesothelium, is closely connected to the endothelium of cerebrovascular vessels and regulates the exchange of substances between cerebrospinal fluid and veins. It is worth noting that the number of immune cells increases in the immune activation state, suggesting that SLYM may play a role in regulating brain immune homeostasis ( Møllgård et al, 2023 ). Overall, there are still many questions about the influence of special structural and functional changes on BBB homeostasis during the perioperative period that have yet to be explained.…”

Section: Potential Pathophysiological Processes and Mechanismsmentioning

confidence: 99%

Research progress on perioperative blood-brain barrier damage and its potential mechanism

Qiu

et al. 2023

Front. Cell Dev. Biol.

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The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

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A mesothelium divides the subarachnoid space into functional compartments

Cited by 130 publications

References 52 publications

Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

Large-scale morphometry of the subarachnoid space of the optic nerve

Research progress on perioperative blood-brain barrier damage and its potential mechanism

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