Protection against hippocampal CA1 cell loss by post-ischemie hypothermia is dependent on delay of initiation and duration

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Abstract
The temporal constraints of protection of neuronal damage by post-ischemic hypothermia was investigated in the gerbil model of global ischemia. Three experimental paradigms were used: 1) Hypothermia was initiated prior to ischemia followed by warming to normothermia immediately post ischemia; 2) Hypothermia of different durations was initiated immediately after reflow and 3) Six hours of hypothermia was initiated at various times following reperfusion. Hypothermia during 5 minutes of ischemia followed by warming to normal body temperature immediately post ischemia resulted in near complete protection of the hippocampus from CA1 cell loss. Hypothermie durations of 1/2, 1, 2, 4, and 6 hours beginning immediately following reperfusion resulted in progressively increased protection from ischemie damage (6±6%, 21±10%, 34±15%, 75±16% and 77±12%, respectively). Six hours of hypothermia delayed for 1 hour after reperfusion resulted in 49±9% protection. No reduction of ischemic damage was observed if 6 hours of hypothermia was delayed for 3 hour after reflow. These data suggest that: 1) Hypothermia during ischemia protects the brain from damage; 2) Hypothermia initiated immediately following reperfusion must have a duration of 2 hours or more to be effective and 3) Six hours of hypothermia is effective if initiated within 1 hour of reperfusion.