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Science. 2020 Jan 30. pii: eaax7171. doi: 10.1126/science.aax7171. [Epub ahead of print]

Cerebrospinal fluid influx drives acute ischemic tissue swelling.

Author information

1
Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
2
Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA.
3
School of Pharmacy, China Medical University, Shenyang 110122, China.
4
Department of Neurosurgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
5
Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
6
Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark.
7
Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA.
8
Department of Pathology, Rush University, Chicago, IL 60612, USA.
9
Rush Alzheimer's Disease Center, Rush University, Chicago, IL 60612, USA.
10
Neurobiology, Biochemistry and Biophysics School, George S. Wise Faculty of Life Sciences, Tel Aviv University, 30 Haim Levanon St., Tel Aviv 69978, Israel.
11
Sagol School for Neuroscience, Tel Aviv University, 30 Haim Levanon St., Tel Aviv 69978, Israel.
12
Department of Physics, University of California, San Diego, La Jolla, CA 92093, USA.
13
Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.
14
Laboratory of Neuron-Glia Circuitry, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
15
Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. maiken_nedergaard@urmc.rochester.edu yuki.mori@sund.ku.dk.
16
Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA. maiken_nedergaard@urmc.rochester.edu yuki.mori@sund.ku.dk.

Abstract

Stroke affects millions each year. Post-stroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents, to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of post-stroke edema needs to be revised and these findings could provide a conceptual basis for development of alternative treatment strategies.

PMID:
32001524
DOI:
10.1126/science.aax7171

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