Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats

Considerable controversy exists about whether postischemic hypothermia can permanently salvage hippocampal CA1 neurons or just postpone injury. Studie s of very brief cooling in rat have found transient benefit, whereas experi ments in gerbil using protracted hypothermia report lasting protection. Thi s discrepancy might be because of the greater efficacy of longer cooling or it might, for example, represent an important species difference. In the p resent study, a 48-hour period of mild hypothermia was induced starting 6 h ours after 10 minutes of severe four-vessel occlusion ischemia in rats. Unt reated normothermic ischemia resulted in total CAI cell loss (99%), whereas delayed hypothermia treatment reduced neuronal loss to 14% at a 28-day sur vival. In unregulated rats, brain temperature spontaneously fell during isc hemia, and stayed subnormal for an extended period after ischemia. This mil d cooling resulted in more variable and less severe CAI injury (75%). Final ly, vertebral artery cauterization under halothane anesthesia caused an app roximately 2 degrees C drop in brain temperature for 1 hour, but prevention of this hypothermia did not significantly affect CA1 damage. In summary, p rotracted postischemic hypothermia provided robust and long-term CAI protec tion in rat. These results encourage the clinical assessment of prolonged h ypothermia and its use as a model to understand ischemic CA1 injury.