Spontaneous spreading depolarizations (SDs) occur in the penumbra surrounding 
ischemic core. These SDs, often referred to as peri-infarct depolarizations, 
cause vasoconstriction and recruitment of the penumbra into the ischemic core in 
the critical first hours after focal ischemic stroke; however, the real-time 
spatiotemporal dynamics of SD-induced injury to synaptic circuitry in the 
penumbra remain unknown. A modified cortical photothrombosis model was used to 
produce a square-shaped lesion surrounding a penumbra-like "area at risk" in 
middle cerebral artery territory of mouse somatosensory cortex. Lesioning 
resulted in recurrent spontaneous SDs. In vivo two-photon microscopy of green 
fluorescent protein-expressing neurons in this penumbra-like area at risk 
revealed that SDs were temporally correlated with rapid (<6 s) dendritic 
beading. Dendrites quickly (<3 min) recovered between SDs to near-control 
morphology until the occurrence of SD-induced terminal dendritic injury, 
signifying acute synaptic damage. SDs are characterized by a breakdown of ion 
homeostasis that can be recovered by ion pumps if the energy supply is adequate. 
Indeed, the likelihood of rapid dendritic recovery between SDs was correlated 
with the presence of nearby flowing blood vessels, but the presence of such 
vessels was not always sufficient for rapid dendritic recovery, suggesting that 
energy needs for recovery exceeded energy supply of compromised blood flow. We 
propose that metabolic stress resulting from recurring SDs facilitates acute 
injury at the level of dendrites and dendritic spines in metabolically 
compromised tissue, expediting penumbral recruitment into the ischemic core.