Basic studies for prevention and treatment of the ischemic neuronal death

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The aim of this study was to investigate whether repetitive sublethal ischemia enhances isehemic tolerance or not. Seventy-two adult male Mongolian gerbils were used. Bilateral carotid arteries were occluded for 2 min to induce sublethal forebrain ischemia, or 4 min to induce lethal ischemia. Sublethal ischemia were given once or eight times (every 2 days or 4 days) to the animals 2 or 4 weeks before lethal ischemia. Seven days after lethal ischemic insult, the animals were perfusion-fixed, and the neuronal densities in the hippocampal CA1 sector were estimated. Twenty-eight animals were used for the immunohistological study. At 2w and 4 w following single or multiple sublethal ischemia (every 2 days) and at 2d following the lethal ischemia immunostaining of fixed gebil brain containing the dorsal hippocampus against HSP7O was performed. In gerbils with repetitive sublethal ischemia, neuronal density of the CA1 sector was significantly (p<O.05) higher at 4 weeks following the last sublethal ischemia than that of the animals with single sublethal ischemia. Induction of HSP7O was seen neither at 2w and 4 w following single or multiple sublethal ischemia (every 2 days) nor at 2d following the lethal ischemia. The present study revealed that repetitive sublethal ischemia enhances ischemic tolerance.In another experiment using 5-mm forebrain iscemia model, effect of indomethacin to the neuronal death in the hippocampal CA1 sector was studied. Indomethacin did not ameliorate neuronal death under the condition that kept brain temperature (temporal muscle temperature) at 37.5 0.5. This study delineated that protective effect of indomethacin to the ischemic neyronal injury is based on the lowering effect of brain temperature.