@article{480d9fbf6d224bca9eed62169a9230ca,
title = "Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading Depolarizations",
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.",
keywords = "cerebral ischemia, laser speckle imaging, middle cerebral artery occlusion, migraine aura, optogenetics",
author = "Kazutaka Sugimoto and Chung, {David Y.} and Maximilian B{\"o}hm and Paul Fischer and Tsubasa Takizawa and {Aslihan Aykan}, Sanem and Tao Qin and Takeshi Yanagisawa and Andrea Harriott and Fumiaki Oka and Yaseen, {Mohammad A.} and Sava Sakad{\v z}i{\'c} and Cenk Ayata",
note = "Funding Information: This work was funded by the National Institutes of Health (R25NS065743, KL2TR002542, and K08NS112601 to Dr Chung and P01NS055104 and R01NS102969 to Dr Ayata); the American Heart Association and American Stroke Association (18POST34030369 to Dr Chung); the Andrew David Heit-man Foundation (Drs Chung and Ayata); the Aneurysm and AVM Foundation (Dr Chung); the Brain Aneurysm Foundation{\textquoteright}s Timothy P. Susco and Andrew David Heitman Foundation Chairs of Research (Dr Chung); the Ellison Foundation (Dr Ayata); the Boehringer Ingelheim Fonds (Dr B{\"o}hm); the Turkish Society of Physical Medicine and Rehabilitation personal fees (Dr Aslihan Aykan); electroCore (Dr Harriott); and the Building Interdisciplinary Careers in Women{\textquoteright}s Health (BIRCWH -K12 5 K12 HD051959 14 to Dr Harriott). Publisher Copyright: {\textcopyright} 2020 The Authors.",
year = "2020",
month = aug,
day = "1",
doi = "10.1161/STROKEAHA.120.029618",
language = "English",
volume = "51",
pages = "2526--2535",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "8",
}