Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading Depolarizations

Kazutaka Sugimoto, David Y. Chung, Maximilian Böhm, Paul Fischer, Tsubasa Takizawa, Sanem Aslihan Aykan, Tao Qin, Takeshi Yanagisawa, Andrea Harriott, Fumiaki Oka, Mohammad A. Yaseen, Sava Sakadžić, Cenk Ayata

Research output: Contribution to journalArticle

Abstract

Background and Purpose: Spreading depolarizations (SDs) are recurrent and ostensibly spontaneous depolarization waves that may contribute to infarct progression after stroke. Somatosensory activation of the metastable peri-infarct tissue triggers peri-infarct SDs at a high rate. Methods: We directly measured the functional activation threshold to trigger SDs in peri-infarct hot zones using optogenetic stimulation after distal middle cerebral artery occlusion in Thy1-ChR2-YFP mice. Results: Optogenetic activation of peri-infarct tissue triggered SDs at a strikingly high rate (64%) compared with contralateral homotopic cortex (8%; P=0.004). Laser speckle perfusion imaging identified a residual blood flow of 31±2% of baseline marking the metastable tissue with a propensity to develop SDs. Conclusions: Our data reveal a spatially distinct increase in SD susceptibility in peri-infarct tissue where physiological levels of functional activation are capable of triggering SDs. Given the potentially deleterious effects of peri-infarct SDs, the effect of sensory overstimulation in hyperacute stroke should be examined more carefully.

Original languageEnglish
Pages (from-to)2526-2535
Number of pages10
JournalStroke
Volume51
Issue number8
DOIs
Publication statusPublished - 2020 Aug 1

Keywords

  • cerebral ischemia
  • laser speckle imaging
  • middle cerebral artery occlusion
  • migraine aura
  • optogenetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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    Sugimoto, K., Chung, D. Y., Böhm, M., Fischer, P., Takizawa, T., Aslihan Aykan, S., Qin, T., Yanagisawa, T., Harriott, A., Oka, F., Yaseen, M. A., Sakadžić, S., & Ayata, C. (2020). Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading Depolarizations. Stroke, 51(8), 2526-2535. https://doi.org/10.1161/STROKEAHA.120.029618