EFFECT OF IMMUNOSUPPRESSANT FK506 ON ISCHEMIA-INDUCED DEGENERATION OFHIPPOCAMPAL-NEURONS IN GERBILS

To evaluate the effect of FK506 on delayed neuronal death in gerbils a fter forebrain ischemia, 84 adult Mongolian gerbils were used in this study. Transient forebrain ischemia was induced by clipping common car otid arteries bilaterally for 5 minutes. One hour after reperfusion, w e intraperitoneally injected FK506 (1.0 mg/kg), cyclosporin A (CsA) (1 0.0 mg/kg) or the vehicle solution into each gerbil. In one group, eac h agent was additionally administered daily 3 more times at 24, 48 and 72 hours after ischemia. The gerbils were killed 4 days or 10 days af ter transient ischemia, and damage to their hippocampal pyramidal cell s was histologically assessed. Additionally, the body temperature was measured following administration of each drug to investigate drug-ind uced hypothermia. Post-ischemic repeated treatment with FK506 signific antly (p<0.01) reduced degeneration of hippocampal neurons. However, p artial treatment did not modify neuronal degeneration CsA did not show a neuroprotective effect in this study. Drug-induced mild hypothermia (35-37 degrees C) was observed following administration of FK506 or C sA. There was no significant difference in the time course of the body temperature between the FK506 and CsA group. We demonstrated that the repeated FK506 treatment, but not the CsA treatment, reduced ischemia -induced degeneration of hippocampal neurons in gerbils. Although FK50 6-induced hypothermia might have modified neuronal degeneration, a com parison with CsA indicated that the neuroprotective effect of FK506 wa s not solely due to hypothermia per se.