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

• Published in: Stroke (1970) Vol. 51; no. 8; pp. 2526 - 2535
• Main Authors: Sugimoto, Kazutaka, Chung, David Y., Böhm, Maximilian, Fischer, Paul, Takizawa, Tsubasa, Aslihan Aykan, Sanem, Qin, Tao, Yanagisawa, Takeshi, Harriott, Andrea, Oka, Fumiaki, Yaseen, Mohammad A., Sakadžić, Sava, Ayata, Cenk
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.08.2020
• Subjects: Animals; Cerebral Infarction - genetics; Cerebral Infarction - physiopathology; Cerebrovascular Circulation - physiology; Cortical Spreading Depression - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Optogenetics - methods; laser speckle imaging; migraine aura; cerebral ischemia; middle cerebral artery occlusion; optogenetics
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.120.029618

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.