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

Brain. 2022 Apr 18;145(2):787-797. doi: 10.1093/brain/awab293.

Authors

Ting Du^{1

2}, Humberto Mestre^{1

3

4}, Benjamin T Kress^{1

5}, Guojun Liu^{1

6}, Amanda M Sweeney¹, Andrew J Samson⁵, Martin Kaag Rasmussen⁵, Kristian Nygaard Mortensen⁵, Peter A R Bork^{5

7}, Weiguo Peng^{1

5}, Genaro E Olveda¹, Logan Bashford⁸, Edna R Toro⁸, Jeffrey Tithof^{8

9}, Douglas H Kelley⁸, John H Thomas⁸, Poul G Hjorth⁷, Erik A Martens^{7

10}, Rupal I Mehta^{1

11}, Hajime Hirase⁵, Yuki Mori⁵, Maiken Nedergaard^{1

5}

Affiliations

¹ Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
² School of Pharmacy, China Medical University, Shenyang 110122, China.
³ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA.
⁴ Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵ Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
⁶ Department of Neurosurgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
⁷ Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark.
⁸ Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA.
⁹ Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
¹⁰ Centre for Mathematical Science, Lund University, 22100 Lund, Sweden.
¹¹ Rush University Alzheimer's Disease Center, Department of Pathology, Rush University, Chicago, IL, USA.

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.

Keywords: anoxic cerebral oedema; cardiac arrest; cerebrospinal fluid; spreading depolarizations.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Brain
Brain Edema* / etiology
Heart Arrest* / complications
Heart Arrest* / therapy
Humans
Hypothermia, Induced*
Hypoxia, Brain* / complications
Mice

Abstract

Publication types

MeSH terms

Grants and funding