DELAYED POSTISCHEMIC HYPOTHERMIA - A 6 MONTH SURVIVAL STUDY USING BEHAVIORAL AND HISTOLOGICAL ASSESSMENTS OF NEUROPROTECTION

In the gerbil, brief global forebrain ischemia induces profound habitu ation and working memory impairments that stem from delayed hippocampa l CA1 death, Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to in vestigate whether prolonged postischemic hypothermia provided long-ter m CA1 and functional neuroprotection. Previously, 90% of anterior CA1 neurons were rescued (30 d survival) when 24 hr of hypothermia (32 deg rees C) was induced 1 hr following a 5 min occlusion that otherwise pr oduced more than 95% loss (Colbourne and Corbett, 1994). We now find a bout 70% CA1 savings with this same hypothermic treatment in gerbils t hat survived for 6 months postischemia. While this is a significant re duction from 30 day survival (medial CA1 only), it nonetheless shows, for the first time, persistent, if not permanent neuroprotection, espe cially in middle and lateral CA1, In addition, in nontreated animals, ischemia impaired learning in an open field and T-maze for up to 6 mon ths. Postischemic hypothermia significantly reduced these deficits, Hy pothermia (32 degrees), when initiated 4 hr after ischemia, rescued ap proximate to 12% of CA1 neurons at 6 months with a slight behavioral b enefit. Milder hypothermia (34 degrees C, 1-25 hr postischemia, 30 d s urvival) also reduced habituation impairments and saved approximate to 60% of CA1 neurons. Similar trends were found at more caudal CA1 leve ls. These results clearly show that postischemic hypothermia provides effective and long-lasting neuroprotection, which depends upon the del ay to initiation, duration, and degree of cooling and survival time. T he protracted functional and histological benefit observed justifies f urther basic and clinical investigation.