THE SEQUENTIAL CHANGE OF LOCAL CEREBRAL BLOOD-FLOW AND LOCAL CEREBRALGLUCOSE-METABOLISM AFTER FOCAL CEREBRAL-ISCHEMIA AND REPERFUSION IN RAT AND THE EFFECT OF MK-801 ON LOCAL CEREBRAL GLUCOSE-METABOLISM

In order to investigate the time course change of local cerebral blood flow (lCBF) and local cerebral glucose metabolism (lCGM) and the effe ct of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose met abolism in a middle cerebral artery occlusion-reperfusion model, C-14- Iodo-antipyrine and C-14-Deoxyglucose autoradiographic method have bee n used. The lCBF was reduced to 0-10% of the control level in the isch aemic core and to 12-40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marke d hyperfusion appeared at 15 min and maintained about 30 to 45 min fol lowing reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reac hed to the peak at 60 min after the middle cerebral artery (MCA) occlu sion both in the ischaemic core and in the penumbra. The shift from hy per-to hypometabolism was observed during the ischaemia. The reperfusi on following 2 hours of MCA occlusion facilitated the decrease of cere bral glucose metabolism in the ischaemic region. The pretreatment of M K-801 (0.4 mg/kg) inhibited both increased glucose metabolism during t he ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfu sion by MK-801 was remarkable in the ischaemic penumbra. These finding s support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.