Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema

Ting Du; Humberto Mestre; Benjamin T. Kress; Guojun Liu; Amanda M. Sweeney; Andrew J. Samson; Martin Kaag Rasmussen; Kristian Nygaard Mortensen; Peter A.R. Bork; Weiguo Peng; Genaro E. Olveda; Logan Bashford; Edna R. Toro; Jeffrey Tithof; Douglas H. Kelley; John H. Thomas; Poul G. Hjorth; Erik A. Martens; Rupal I. Mehta; Hajime Hirase; Yuki Mori; Maiken Nedergaard

doi:10.1093/brain/awab293

Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema

Ting Du, Humberto Mestre, Benjamin T. Kress, Guojun Liu, Amanda M. Sweeney, Andrew J. Samson, Martin Kaag Rasmussen, Kristian Nygaard Mortensen, Peter A.R. Bork, Weiguo Peng, Genaro E. Olveda, Logan Bashford, Edna R. Toro, Jeffrey Tithof, Douglas H. Kelley, John H. Thomas, Poul G. Hjorth, Erik A. Martens, Rupal I. Mehta, Hajime HiraseYuki Mori, Maiken Nedergaard

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20 Scopus citations

Abstract

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Original language	English (US)
Pages (from-to)	787-797
Number of pages	11
Journal	Brain
Volume	145
Issue number	2
DOIs	https://doi.org/10.1093/brain/awab293
State	Published - Feb 1 2022
Externally published	Yes

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Publisher Copyright:
© 2021 The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Keywords

anoxic cerebral oedema
cardiac arrest
cerebrospinal fluid
spreading depolarizations

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Du, T., Mestre, H., Kress, B. T., Liu, G., Sweeney, A. M., Samson, A. J., Rasmussen, M. K., Mortensen, K. N., Bork, P. A. R., Peng, W., Olveda, G. E., Bashford, L., Toro, E. R., Tithof, J., Kelley, D. H., Thomas, J. H., Hjorth, P. G., Martens, E. A., Mehta, R. I., ... Nedergaard, M. (2022). Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema. Brain, 145(2), 787-797. https://doi.org/10.1093/brain/awab293

Du, T, Mestre, H, Kress, BT, Liu, G, Sweeney, AM, Samson, AJ, Rasmussen, MK, Mortensen, KN, Bork, PAR, Peng, W, Olveda, GE, Bashford, L, Toro, ER, Tithof, J, Kelley, DH, Thomas, JH, Hjorth, PG, Martens, EA, Mehta, RI, Hirase, H, Mori, Y & Nedergaard, M 2022, 'Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema', Brain, vol. 145, no. 2, pp. 787-797. https://doi.org/10.1093/brain/awab293

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Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema

Abstract

Bibliographical note

Keywords

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