N-G-NITRO-L-ARGININE-METHYL-ESTER PROTECTS AGAINST ISCHEMIA-INDUCED BIOCHEMICAL-CHANGES AND HIPPOCAMPAL NEURODEGENERATION IN THE GERBIL

To assess the effects of the nitric oxide inhibitor N-G-nitro-L-argini ne methyl ester (L-NAME) on behavioural, biochemical and histological changes following global ischaemia, the Mongolian gerbil was used. Isc haemia was induced by bilateral carotid occlusion (BCO) for 5 min. N-G -nitro-L-arginine methyl ester was administered i.p. at 10 mg/kg 30 mi n, 6, 24, and 48 h after surgery. Results indicated that 5 min BCO cau sed a large increase in home cage activity. N-G-nitro-L-arginine methy l ester caused some attenuation in this hyperactivity. The activity of nitric oxide synthase (NOS) was increased in the cerebellum, brain st em, striatum, cerebral cortex and hippocampus of 5-min bilateral carot id occluded animals. N-G-nitro-L-arginine methyl ester reversed the in crease in nitric oxide synthase activity in all brain regions. Extensi ve neuronal death was observed in the CA(1) layer of the hippocampus i n 5-min BCO animals 96 h after surgery. N-G-nitro-L-arginine methyl es ter significantly protected against the neuronal death of cells in the CA(1) layer.