Rapid hematoma growth triggers spreading depolarizations in experimental intracortical hemorrhage

Paul Fischer, Kazutaka Sugimoto, David Y. Chung, Isra Tamim, Andreia Morais, Tsubasa Takizawa, Tao Qin, Carlos A. Gomez, Frieder Schlunk, Matthias Endres, Mohammad A. Yaseen, Sava Sakadzic, Cenk Ayata

Research output: Contribution to journalArticlepeer-review

Abstract

Recurrent waves of spreading depolarization (SD) occur in brain injury and are thought to affect outcomes. What triggers SD in intracerebral hemorrhage is poorly understood. We employed intrinsic optical signaling, laser speckle flowmetry, and electrocorticography to elucidate the mechanisms triggering SD in a collagenase model of intracortical hemorrhage in mice. Hematoma growth, SD occurrence, and cortical blood flow changes were tracked. During early hemorrhage (0–4 h), 17 out of 38 mice developed SDs, which always originated from the hematoma. No SD was detected at late time points (8–52 h). Neither hematoma size, nor peri-hematoma perfusion were associated with SD occurrence. Further, arguing against ischemia as a trigger factor, normobaric hyperoxia did not inhibit SD occurrence. Instead, SDs always occurred during periods of rapid hematoma growth, which was two-fold faster immediately preceding an SD compared with the peak growth rates in animals that did not develop any SDs. Induced hypertension accelerated hematoma growth and resulted in a four-fold increase in SD occurrence compared with normotensive animals. Altogether, our data suggest that spontaneous SDs in this intracortical hemorrhage model are triggered by the mechanical distortion of tissue by rapidly growing hematomas.

Original languageEnglish
Pages (from-to)1264-1276
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume41
Issue number6
DOIs
Publication statusPublished - 2021 Jun
Externally publishedYes

Keywords

  • Cerebral amyloid angiopathy
  • electrocorticography
  • intracerebral hemorrhage
  • laser speckle imaging
  • spreading depolarization

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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