PRETREATMENT BUT NOT POSTTREATMENT WITH GYKI-52466 REDUCES FUNCTIONALDEFICITS AND NEURONAL DAMAGE AFTER GLOBAL-ISCHEMIA IN RATS

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of t he present study was to investigate the potential neuroprotective effe ct of GYKI 52466, an antagonist at the non-N-methyl-D-aspartate recept or, with behavioural and histological measures of global ischemia in r ats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 mi n before induction of ischemia or immediately after onset of reperfusi on. One week after surgery spatial learning was tested in the Morris w ater maze. After behavioural testing the animals were sacrificed and t he neuronal damaged was assessed. GYKI 52466 reduced the increase in e scape latency and in swim distance induced by 4VO when given before is chemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuate d by pretreatment but not by posttreatment with GYKI 52466. Striatal n euronal damage was not affected by either treatment with GYKI 52466. G YKI 52466 had neuroprotective effects in a rat model of global cerebra l ischemia. Pretreatment with GYKI 52466 protected rats against behavi oural deficits and hippocampal neuronal damage induced by 4VO.