INTRAISCHEMIC BUT NOT POSTISCHEMIC BRAIN HYPOTHERMIA PROTECTS CHRONICALLY FOLLOWING GLOBAL FOREBRAIN ISCHEMIA IN RATS

We investigated whether postischemic brain hypothermia (30-degrees-C) would permanently protect the hippocampus following global forebrain i schemia. Global ischemia was produced in anesthetized rats by bilatera l carotid artery occlusion plus hypotension (50 mm Hg). In the postisc hemic hypothermic group, brain temperature was maintained at 37-degree s-C during the 10-min ischemic insult but reduced to 30-degrees-C star ting 3 min into the recirculation period and maintained at 30-degrees- C for 3 h. In normothermic animals, intra- and postischemic brain temp erature was maintained at 37-degrees-C. After recovery for 3 days, 7 d ays, or 2 months, the extent of CA1 hippocampal histologic injury was quantitated. At 3 days after ischemia, postischemic hypothermia signif icantly protected the hippocampal CA1 sector compared with normothermi c animals. For example, within the medial, middle, and lateral CA1 sub sectors, the numbers of normal neurons were increased 20-, 13-, and 9- fold by postischemic hypothermia (p < 0.01). At 7 days after the ische mic insult, however, the degree of postischemic hypothermic protection was significantly reduced. In this case, the numbers of normal neuron s were increased an average of only threefold compared with normotherm ia. Ultrastructural analysis of 7-day postischemic hypothermic rats de monstrated CA1 pyramidal neurons showing variable degrees of injury su rrounded by reactive astrocytes and microglial cells. At 2 months afte r the ischemic insult, no trend for protection was demonstrated. In co ntrast to postischemic hypothermia, significant protection was seen at 2 months following intraischemic hypothermia. These data indicate tha t intraischemic, but not postischemic, brain hypothermia provides chro nic protection to the hippocampus after transient brain ischemia. The inability of postischemic hypothermia to protect chronically after 3 d ays could indicate that (a) postischemic hypothermia merely delays isc hemic cell death and/or (b) the postischemic brain undergoes a seconda ry insult. In postischemic treatment protocols, chronic survival studi es are required to determine accurately the ultimate histopathological outcome following global cerebral ischemia.