The objective of this study was to define the degree of hypothermia required to diminish ischemic injury to CA1 hippocampal neurons following 5-min bilateral ischemia in the gerbil. The temperature of the body and head was regulated in three groups of animals at 37.5, 35.5, or 32.5°C during 5-min bilateral carotid artery occlusion. Upon recirculation, normothermia was restored in all animals, and recovery was permitted for 1 week. Ischemic injury to CA1 hippocampus was determined using three endpoints: histologic injury, ATP content, and adenylate kinase activity. Reduction of head temperature to 35.5 and 32.5°C during ischemia diminished histologic injury and improved CA1 levels of ATP and adenylate kinase activity in a dose-dependent manner. Indeed, 32.5°C completely abolished ischemic injury to CA1 hippocampus, judging from each of the three endpoints. Reduction of head temperature to 32.5°C delayed but did not prevent the depletion of ATP throughout the hippocampus during the 5-min ischemic insult. These results demonstrate that a decrease in head temperature of only 2°C reduces the degree of CA1 injury in the gerbil model of 5-min bilateral ischemia. Thus, it is imperative to maintain strict normothermia in pharmacologic studies of ischemic protection. Finally, administration of nicardipine to normothermic gerbils failed to diminish ischemic injury in the CA1 hippocampus.
Blockade of HCN2 Channels Provides Neuroprotection Against Ischemic Injury via Accelerating Autophagic Degradation in Hippocampal Neurons