BEHAVIORAL-TESTING DOES NOT EXACERBATE ISCHEMIC CA1 DAMAGE IN GERBILS

Background and Purpose-Previous research studying ablative lesions has suggested that functional use may exacerbate brain injury. If true, t his would have considerable ramifications not only for the mechanistic understanding of neuronal injury but also for the clinical use of phy siotherapy. In this report the hypothesis that behavioral use of brain tissue exacerbates ischemic hippocampal injury was tested. Methods-Ge rbils were subjected to sham operation or 5 minutes of normothermic is chemia. To produce borderline hippocampal CA1 injury and enhance susce ptibility to exacerbation, 2 of 3 ischemic groups were cooled (>48 hou rs) beginning at 6 hours after ischemia. Increased use of the hippocam pus was produced by a battery of tests involving 3 novel small mazes, a T maze, and an open field. One hypothermic group was not tested and served as a control. Results-Behavioral testing failed to worsen ische mic damage since neuronal loss in the behaviorally tested and untested hypothermic groups was 12% and 8%, respectively, while that in the un treated ischemic group was 81% at a 1-month survival. Accordingly, pro tected CA1 cells tolerated the neuronal activity associated with behav ioral testing. Concomitant with marked CA1 neuroprotection, a signific ant reduction in behavioral deficits with the hypothermic treatment wa s observed. Importantly, behavioral testing was found to transiently e levate brain temperature. Conclusions-CA1 neuronal survival was unaffe cted by behavioral testing or the associated mild fever. Hypothermia d elayed for 6 hours provided sustainable CA1 neuroprotection.