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

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. Hypothermic durations of 1/2, 1, 2, 4, and 6 hours beginning immediately following reperfusion resulted in progressively increased protection from ischemic 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.