Injury depolarizations triggered by supply-demand mismatch

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Contratulations to Daniel von Bornstadt and collegues on publishing this landmark paper in Neuron (Vol 85 Issue 5, p1117-1131, 2015). This is the first work to directly address, and document with extensive experiments, why and how spreading injury depolarizations (or PIDs) occur in ischemic penumbra.  This study clearly shows that depolarizations, while appearing spontaneous, arise when energy supply-demand mismatches occur in a narrow penumbral ‘hot-zone’, thereby depleting local tissue oxygen and tipping the balance toward ionic failure.  Particularly interesting is that 2 hot-zones are identified. In the inner band (lower blood flow) with electrical silence, depolarization can be triggered by hypoxia or hypotension.  In the outer hot-zone where there is still synaptic activity (higher blood flow), depolarizations can be elicited by sensory stimulation in areas that map to the cortical hot-zone, thereby increasing metabolic demand. While many important past findings and suspicions are confirmed here, this paper offers a completely new finding with clear clinical implications: a patient’s environment and external stimuli may influence his/her recovery.  Follow the Neuron link above for the video abstract.

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