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

Abstract

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. 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. Optogenetic activation of peri-infarct tissue triggered SDs at a strikingly high rate (64%) compared with contralateral homotopic cortex (8%; <i>P</i>=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. 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.