Abstract
The dura, arachnoid and pia mater, as the constituent layers of the meninges, along with cerebrospinal fluid in the subarachnoid space and ventricles, are essential protectors of the brain and spinal cord. Complemented by immune cells, blood vessels, lymphatic vessels and nerves, these connective tissue layers have held many secrets that have only recently begun to be revealed. Each meningeal layer is now known to have molecularly distinct types of fibroblasts. Cerebrospinal fluid clearance through peripheral lymphatics and lymph nodes is well documented, but its routes and flow dynamics are debated. Advances made in meningeal immune functions are also debated. This Review considers the cellular and molecular structure and function of the dura, arachnoid and pia mater in the context of conventional views, recent progress, and what is uncertain or unknown. The hallmarks of meningeal pathophysiology are identified toward developing a more complete understanding of the meninges in health and disease.
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Acknowledgements
This work was supported in part by funding from the Swedish Research Council (2015-00550, to C.B.); Swedish Cancer Society (2018/449, 2018/1154 and 211714Pj, to C.B.); Knut and Alice Wallenberg Foundation (2020.0057, to C.B.); Swedish Brain Foundation (ALZ2019-0130 and ALZ2022-0005, to C.B.); Erling-Persson Family Foundation (to C.B.); Leducq Foundation (22CVD01 and 23CVD02, to C.B.) Fidelity Bermuda Foundation (to S.T.P. and B.E.); Swiss National Science Foundation (310030_189080, to B.E.; 310030_189226, to S.T.P.; and CRSII5_213535, to S.T.P. and B.E.); Republic of Korea Ministry of Science and Information and Communication Technology to the Institute for Basic Science (IBS-R025-D1-2015, to G.Y.K.); National Heart, Lung, and Blood Institute grants (R01 HL143896, R01 HL059157 and R01 HL127402, to D.M.D.); and National Institute of Neurological Disorders and Stroke grant (R01 NS098273, to J.S.) from the US National Institutes of Health. We thank H. J. Shin for drawing Fig. 1.
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C.B., B.E., G.Y.K., D.M.D., S.T.P. and J.S. conceived the theme, scope and structure of the review, wrote the manuscript and drafted the figures.
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Betsholtz, C., Engelhardt, B., Koh, G.Y. et al. Advances and controversies in meningeal biology. Nat Neurosci 27, 2056–2072 (2024). https://doi.org/10.1038/s41593-024-01701-8
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DOI: https://doi.org/10.1038/s41593-024-01701-8
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