Intraischemic mild hypothermia increases hippocampal CA1 blood flow during forebrain ischemia

Abstract

The hippocampal CA1 sector is selectively vulnerable to forebrain ischemia but protected by mild hypothermia. However, the consequence of intraischemic hypothermia on CA1 blood flow during the insult has not been adequately characterized. The effects of mild intraischemic hypothermia on relative changes in regional hippocampal CA1 blood flow were recorded continuously using laser Doppler flowmetry (LDF) during and 30 min after 6 min of forebrain ischemia. Six experimental groups ( n=6/group) of fasted male Wistar rats were compared. Groups 1, 3 and 5 consisted of normothermic rats that underwent either 6 (for CBF measurements) and 6 or 10 (for 7 day survival–CA1 neuronal death measurements) min of transient forebrain ischemia using bilateral carotid clamping and hemorrhagic hypotension. Groups 2, 4 and 6 rats were subjected to mild hypothermia (34°C) before, during, and 30 min after 6 (for CBF measurements) and 6 or 10 (for 7 day survival–CA1 neuronal death measurements) min of transient forebrain ischemia. CA1 blood flow and electroencephalogram (EEG) were continuously recorded. During the ischemic insult there were intergroup differences in the magnitude of CBF decreases in the CA1 region. In both groups 1 and 2, CBF returned to preischemic values within 1 min of reperfusion but hypothermic rats had more sustained hyperemia. Hypothermic rats had a quicker recovery of EEG activity and less delayed CA1 neuronal death (group 2 versus 4). These data suggest ischemic blood flow to the CA1 sector was altered by intraischemic mild hypothermia which may contribute to the greater benefit of intraischemic hypothermic neuroprotection.