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Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origin of spreading injury depolarizations #MMPMID25741731
von Bornstädt D; Houben T; Seidel J; Zheng Y; Dilekoz E; Qin T; Sandow N; Kura S; Eikermann-Haerter K; Endres M; Boas DA; Moskowitz MA; Lo EH; Dreier JP; Woitzik J; Sakad?i? S; Ayata C
Neuron 2015[Mar]; 85 (5): 1117-31 PMID25741731show ga
Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes to PIDs in human stroke as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome.