NG-Nitro-L-Arginine-Methyl-Ester Protects against Ischaemia-Induced Biochemical Changes and Hippocampal Neurodegeneration in the Gerbil

To assess the effects of the nitric oxide inhibitor N^G-nitro-l -arginine methyl ester (L-NAME) on behavioural, biochemical and histological changes following global ischaemia, the Mongolian gerbil was used. Ischaemia 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 min, 6, 24, and 48 h after surgery. Results indicated that 5 min BCO caused a large increase in home cage activity. N^G-nitro-l -arginine methyl ester caused some attenuation in this hyperactivity. The activity of nitric oxide synthase (NOS) was increased in the cerebellum, brain stem, striatum, cerebral cortex and hippocampus of 5-min bilateral carotid occluded animals. N^G-nitro-l -arginine methyl ester reversed the increase in nitric oxide synthase activity in all brain regions. Extensive neuronal death was observed in the CA₁ layer of the hippocampus in 5-min BCO animals 96 h after surgery. N^G-nitro-l -arginine methyl ester significantly protected against the neuronal death of cells in the CA₁ layer.