CHARACTERIZATION OF POSTISCHEMIC BEHAVIORAL DEFICITS IN GERBILS WITH AND WITHOUT HYPOTHERMIC NEUROPROTECTION

Five minutes of global ischemia in gerbil results in delayed hippocamp al CA1 neuronal degeneration, which is accompanied by working memory i mpairments and hyperactivity in novel environments. In this study, pos tischemic activity was characterized in familiar and in novel environm ents to determine whether hyperactivity was due to impaired spatial ha bituation or another form of motor hyperactivity. This study also dete rmined whether 6-h delayed hypothermia, which reduces CA1 neuronal inj ury, would attenuate functional impairments. Gerbils were subjected to 5 min of normothermic ischemia or sham operation 2 days following imp lantation of brain temperature probes. One of two ischemic groups was cooled (> 48 h) starting at 6-h postischemia. Locomotor activity in a familiar cage was measured for 6 days while activity in three novel en vironments was intermittently measured on days 4, 5 and 6. Open field behavior and working memory in a T-maze were also assessed. Untreated ischemia caused marked hyperactivity in the familiar cage on day 1, wh ich reverted to near-normal by day 2. Nonetheless, these gerbils showe d hyperactivity during novel environment sessions on days 4-6. This ma ze behavior, which predicted hippocampal CA1 injury, was not due to di fferent habituation rates nor baseline hyperactivity. Conversely, open field sessions on day 8 revealed ischemic habituation rate deficits. Ischemia also impaired working memory in the T-maze. Delayed hypotherm ia, which reduced neuronal loss in the CA1 sector to 12% from 81%, red uced all functional impairments. Ischemic gerbils quickly developed sp ontaneous locomotion hyperactivity that returned to near-normal after 1 day. This motor hyperactivity did not explain the elevated activity found with delayed testing in novel environments. Regardless, only the open field test on day 8 revealed a habituation-like deficit. (C) 199 8 Elsevier Science B.V. All rights reserved.