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 promisingmethods for neuroprotection in cerebral ischemia. However, the efficacyof superficial LTH at clinically relevant delays after the onsetof ischemic attack remains poorly understood. In the present study,we investigated the neuroprotective effects of LTH in a model offocal ischemia induced by epipial application of the vasoconstrictor Endothelin-1in the somatosensory cortex region of the rat brain. The neuroprotectiveeffects of LTH were assessed by the level of spontaneous and sensory-evokedelectrical activity at different cortical depths using linear electrodearrays. We found that cooling the cortical surface to 28°C usinga Peltier element starting from 0, 10, and 60 minutes after Endothelin-1application caused a significant reduction in the degree of suppressionof electrical activity in the ischemic focus formed in the cerebralcortex 3 hours after Endothelin-1 application. The neuroprotectiveeffects of LTH were manifested by a higher level of spontaneousmultiunit activity, higher power of the local field potential oscillationsin theta, alpha and beta bands, as well in a greater amplitude andhigher multiunit activity during sensory evoked responses. The neuroprotectiveeffects of LTH were inversely correlated with the delay of LTH onsetand were most pronounced with LTH initiated with minimal (0 and10 minutes) delay after Endothelin-1 application. We also foundthat only LTH initiated simultaneously with Endothelin-1 application delayedthe onsets of spreading depolarization waves and that LTH did notaffect the amplitude of negative ultraslow potentials evoked byEndothelin-1. Taken together, the results of the electrophysiologicalanalysis suggest neuroprotective effects of surface LTH, which areparticularly pronounced when LTH is minimally delayed from the onsetof the ischemic insult in the Endothelin-1-induced focal ischemiamodel.