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Updated: Dec 15, 2025
Combining Imaging and Electrophysiology to Visualize and Record Spreading Depolarizations in Mice
Published on: October 4, 2024
Peri-Infarct Hot-Zones Have Higher Susceptibility to Optogenetic Functional Activation-Induced Spreading
Kazutaka Sugimoto1,2, David Y Chung1,3, Maximilian Böhm1
1Department of Radiology (K.S., D.Y.C., M.B., P.F., T.T., S.A.A., T.Q., T.Y., F.O., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
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.
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