Structural characterization of SLYM—a 4th meningeal membrane

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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 4th 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.
OriginalsprogEngelsk
Artikelnummer93
TidsskriftFluids and Barriers of the CNS
Vol/bind20
Udgave nummer1
Antal sider18
ISSN2045-8118
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We acknowledge P. S. Froh (Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark) for excellent technical assistance with the histology and immunohistochemistry of the decalcified samples. We also thank D. Xue for expert graphical support.

Funding Information:
Funding was provided by Lundbeck Foundation grant R386-2021-165 (M.N.), Novo Nordisk Foundation grant NNF20OC0066419 (M.N.), the Vera & Carl Johan Michaelsen’s Legat Foundation (K.M.), National Institutes of Health grant R01AT011439 (M.N.), National Institutes of Health grant U19NS128613 (M.N.), US Army Research Office grant MURI W911NF1910280 (M.N.), Human Frontier Science Program grant RGP0036 (M.N.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.N.), and Simons Foundation grant 811237 (M.N.). The views and conclusions contained in this article are solely those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the National Institutes of Health, the Army Research Office, or the US Government. The US Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein. The funding agencies have taken no part on the design of the study, data collection, analysis, interpretation, or in writing of the manuscript.

Publisher Copyright:
© 2023, The Author(s).

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