Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents

Fumiaki Oka, Ulrike Hoffmann, Jeong Hyun Lee, Hwa Kyoung Shin, David Y. Chung, Izumi Yuzawa, Shih Pin Chen, Yahya B. Atalay, Ala Nozari, Kristen Park Hopson, Tao Qin, Cenk Ayata

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Spontaneous spreading depolarizations are frequent after various forms of human brain injury such as ischemic or hemorrhagic stroke and trauma, and worsen the outcome. We have recently shown that supply-demand mismatch transients trigger spreading depolarizations in ischemic stroke. Here, we examined the mechanisms triggering recurrent spreading depolarization events for many days after subarachnoid hemorrhage. Despite large volumes of subarachnoid hemorrhage induced by cisternal injection of fresh arterial blood in rodents, electrophysiological recordings did not detect a single spreading depolarization for up to 72 h after subarachnoid hemorrhage. Cortical susceptibility to spreading depolarization, measured by direct electrical stimulation or topical KCl application, was suppressed after subarachnoid hemorrhage. Focal cerebral ischemia experimentally induced after subarachnoid hemorrhage revealed a biphasic change in the propensity to develop peri-infarct spreading depolarizations. Frequency of peri-infarct spreading depolarizations decreased at 12 h, increased at 72 h and normalized at 7 days after subarachnoid hemorrhage compared with sham controls. However, ischemic tissue and neurological outcomes were significantly worse after subarachnoid hemorrhage even when peri-infarct spreading depolarization frequency was reduced. Laser speckle flowmetry implicated cerebrovascular hemodynamic mechanisms worsening the outcome. Altogether, our data suggest that cerebral ischemia is required for spreading depolarizations to be triggered after subarachnoid hemorrhage, which then creates a vicious cycle leading to the delayed cerebral ischemia syndrome.

Original languageEnglish (US)
Pages (from-to)1829-1840
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number5
StatePublished - May 1 2017
Externally publishedYes


  • Subarachnoid hemorrhage
  • delayed cerebral ischemia
  • middle cerebral artery occlusion
  • peri-infarct depolarization
  • spreading depolarization

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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