HYPOGLYCEMIA, HYPOXIA, AND ISCHEMIA IN A CORTICOSTRIATAL SLICE PREPARATION - ELECTROPHYSIOLOGIC CHANGES AND ASCORBYL RADICAL FORMATION

Experimental and clinical data suggest that oxygen and/or glucose depr ivation alters electrical transmission in the brain and generates free radicals, which may mediate neuronal death. We have analyzed the effe cts of oxygen and/or glucose deprivation on both excitatory transmissi on, by measuring field potential amplitude, and free radical productio n, by using electron spin resonance (ESR) spectroscopy, in a corticost riatal slice preparation. Combined oxygen and/or glucose deprivation ( ischemia) lasting 10 to 20 minutes induced a long-term depression of f ield potential amplitude. The ascorbyl radical could only be detected in brain slices during the reperfusion-phase after 30 minutes of ische mia. It appeared in the early minutes after the washout of ischemic me dium and remained stable throughout the reperfusion phase. This radica l was never detected in the external medium. Ischemia induced only a s light, but progressive, release of lactate dehydrogenase (LDH) into th e external medium during the reperfusion phase. In contrast, exposure of slices to hypoxia or hypoglycemia alone resulted in transient depre ssion of field potential amplitude, and no generation of ascorbyl radi cals was observed on reperfusion. We propose that the long-lasting los s of electrical signals is the early sign of neuronal damage during is chemia. On the other hand, ascorbyl radical formation may be considere d an indicator of neuronal injury after prolonged energy deprivation.