NEUROPROTECTION AFTER SEVERAL DAYS OF MILD, DRUG-INDUCED HYPOTHERMIA

Stroke trials are initiated after demonstrated pharmacological protect ion in animal models. NBQX protects CA(1) neurons against global ische mia; however, this glutamate antagonist induces a period of subnormal temperature (e.g., a decrease of only 1.0-1.5 degrees C) lasting sever al days. In this study, NBQX (3 x 30 mg/kg, i.p.) was administered sta rting 60 min after reperfusion, and brain temperature had declined sig nificantly below vehicle-treated animals by 2 h after reperfusion. Whe n the postischemic brain temperature of NBQX-treated gerbils was regul ated, no neuronal protection was found. Mimicking an NBQX-induced temp erature profile for 28 h postischemia yielded histological protection 4 days later comparable to that of NBQX. However, both the NBQX and te mperature simulation groups showed decreased protection after 10-day s urvival. Our data suggest that a protracted period of subnormal temper ature during the postischemic period can obscure the interpretation of preclinical drug studies.