N-G-NITRO-L-ARGININE PROTECTS AGAINST ISCHEMIA-INDUCED INCREASES IN NITRIC-OXIDE AND HIPPOCAMPAL NEURO-DEGENERATION IN THE GERBIL

To assess the effects of the nitric oxide synthase inhibitor N-G-Nitro-L-arginine on behavioural, biochemical and histological changes following global ischaemia, the Mongolian gerbil was used. Ischaemia was induced by bilateral carotid occlusion for 5 min. N-G-Nitro-L-arginine was administered i.p. at either 1 or 10 mg/kg 30 min, 6, 24, and 48 h after surgery. 5 min bilateral carotid occluded animals were hyperactive 24, 48 and 72 h after surgery. N-G-Nitro-L-arginine caused some attenuation in this hyperactivity. The activity of nitric oxide synthase was increased in the cerebellum, brain stem, striatum, cerebral cortex and hippocampus of 5 min bilateral carotid occluded animals. N-G-Nitro-L-aginine reversed the increase in nitric oxide synthase activity in all brain regions. Extensive neuronal death was observed in the CA(1) layer of the hippocampus in 5 min bilateral carotid occluded animals 96 h after surgery. N-G-Nitro-L-arginine significantly protected against the neuronal death of cells in the CA(1) layer.