Cerebrospinal fluid influx drives acute ischemic tissue swelling

Humberto Mestre, Ting Du, Amanda M Sweeney, Guojun Liu, Andrew J Samson, Weiguo Peng, Kristian Nygaard Mortensen, Frederik Filip Stæger, Peter Aleksander Rousing Bork, Logan Bashford, Edna R Toro, Jeffrey Tithof, Douglas H Kelley, John H Thomas, Poul G. Hjorth, Erik Andreas Martens, Rupal I Mehta, Orestes Solis, Pablo Blinder, David KleinfeldHajime Hirase, Yuki Mori, Maiken Nedergaard*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalScience
Number of pages24
ISSN0036-8075
DOIs
Publication statusPublished - 2020

Cite this

Mestre, H., Du, T., Sweeney, A. M., Liu, G., Samson, A. J., Peng, W., ... Nedergaard, M. (2020). Cerebrospinal fluid influx drives acute ischemic tissue swelling. Science. https://doi.org/10.1126/science.aax7171