Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome

Kazutaka Sugimoto, Joanna Yang, Paul Fischer, Tsubasa Takizawa, Inge A. Mulder, Tao Qin, Taylan D. Erdogan, Mohammad A. Yaseen, Sava Sakadžić, David Y. Chung, Cenk Ayata

研究成果: Article査読


Background: Spreading depolarizations (SDs) are believed to contribute to injury progression and worsen outcomes in focal cerebral ischemia because exogenously induced SDs have been associated with enlarged infarct volumes. However, previous studies used highly invasive methods to trigger SDs that can directly cause tissue injury (eg, topical KCl) and confound the interpretation. Here, we tested whether SDs indeed enlarge infarcts when induced via a novel, noninjurious method using optogenetics. Methods: Using transgenic mice expressing channelrhodopsin-2 in neurons (Thy1-ChR2-YFP), we induced 8 optogenetic SDs to trigger SDs noninvasively at a remote cortical location in a noninjurious manner during 1-hour distal microvascular clip or proximal an endovascular filament occlusion of the middle cerebral artery. Laser speckle imaging was used to monitor cerebral blood flow. Infarct volumes were then quantified at 24 or 48 hours. Results: Infarct volumes in the optogenetic SD arm did not differ from the control arm in either distal or proximal middle cerebral artery occlusion, despite a 6-fold and 4-fold higher number of SDs, respectively. Identical optogenetic illumination in wild-type mice did not affect the infarct volume. Full-field laser speckle imaging showed that optogenetic stimulation did not affect the perfusion in the peri-infarct cortex. Conclusions: Altogether, these data show that SDs induced noninvasively using optogenetics do not worsen tissue outcomes. Our findings compel a careful reexamination of the notion that SDs are causally linked to infarct expansion.

出版ステータスPublished - 2023 4月 1

ASJC Scopus subject areas

  • 臨床神経学
  • 循環器および心血管医学
  • 高度および特殊看護


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