Cerebrospinal fluid influx drives acute ischemic tissue swelling

Research output: Contribution to journalJournal articlepeer-review

  • Humberto Mestre
  • Ting Du
  • Amanda M. Sweeney
  • Guojun Liu
  • Andrew J. Samson
  • Weiguo Peng
  • Kristian Nygaard Mortensen
  • Logan Bashford
  • Edna R. Toro
  • Jeffrey Tithof
  • Douglas H. Kelley
  • John H. Thomas
  • Poul G. Hjorth
  • Erik A. Martens
  • Rupal I. Mehta
  • Orestes Solis
  • Pablo Blinder
  • David Kleinfeld

Stroke affects millions each year. Poststroke 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 poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.

Original languageEnglish
Article numbereaaw7462
JournalScience
Volume367
Issue number6483
Number of pages8
ISSN0036-8075
DOIs
Publication statusPublished - 2020

ID: 238530939