Neuroprotective Effects of Local Surface Hypothermia during Endothelin-1-Induced Focal Ischemia in Rat Cerebral Cortex. I. Electrophysiological Analysis

Local therapeutic hypothermia (LTH) is one of the most promising methods for neuroprotection in cerebral ischemia. However, the efficacy of superficial LTH at clinically relevant delays after the onset of ischemic attack remains poorly understood. In the present study, we investigated the neuroprotective effects of LTH in a model of focal ischemia induced by epipial application of the vasoconstrictor Endothelin-1 in the somatosensory cortex region of the rat brain. The neuroprotective effects of LTH were assessed by the level of spontaneous and sensory-evoked electrical activity at different cortical depths using linear electrode arrays. We found that cooling the cortical surface to 28°C using a Peltier element starting from 0, 10, and 60 minutes after Endothelin-1 application caused a significant reduction in the degree of suppression of electrical activity in the ischemic focus formed in the cerebral cortex 3 hours after Endothelin-1 application. The neuroprotective effects of LTH were manifested by a higher level of spontaneous multiunit activity, higher power of the local field potential oscillations in theta, alpha and beta bands, as well in a greater amplitude and higher multiunit activity during sensory evoked responses. The neuroprotective effects of LTH were inversely correlated with the delay of LTH onset and were most pronounced with LTH initiated with minimal (0 and 10 minutes) delay after Endothelin-1 application. We also found that only LTH initiated simultaneously with Endothelin-1 application delayed the onsets of spreading depolarization waves and that LTH did not affect the amplitude of negative ultraslow potentials evoked by Endothelin-1. Taken together, the results of the electrophysiological analysis suggest neuroprotective effects of surface LTH, which are particularly pronounced when LTH is minimally delayed from the onset of the ischemic insult in the Endothelin-1-induced focal ischemia model.