Effect of L-arginine and NG-nitro-L-arginine on delayed neuronal death in the gerbil hippocampus

Abstract

To assess the role of nitric oxide (NO) in cerebral ischemia, we investigated the effect of L-arginine, a substrate of NO synthase (NOS), and NG-nitro-L-arginine (L-NNA), a NOS inhibitorl on neuronal death in the CA1 hippocampal region. Seventy-two Mongolian gerbils were used in the study. Both carotid arteries were occluded for 4 min to induce forebrain ischemia. Temporal muscle temperature was strictly maintained at 37.5±0.3°C during the ischemia. L-arginine (70 and 100 mg kg-1) or L-NNA (11 10 and 100 mg kg-1) was administered intraperitoneally 4 times: 30 min beforel 3h, 6h and 24h after induction of ischemia. Four days after ischemic insultl the animals were perfusion-fixed, and the neuronal densities in the media, middle and lateral CA1 subfield were estimated. A verage neuronal cell density of the control group was 2-3 mm in each subfield. L-arginine at doses of 10 and 100 mg kg-1 did not prevent neuronal death. L-NNA at doses of 1 and 10 mg kg-1 did not protect neuronal cells from ischemia either. Howeverl in ischemia gerbils treated with 100 mg kg-1 L-NNAI the average neuronal cell density in the lateral CA 1 subfield was 54.4± 19.1. L-NNA (100 mg kg-1) significantly (p< O. 05) reduced the occurrence of neuronal death in the lateral CA1 subfield. The present results suggest that NO plays an important role in the development of neuronal injury after global ischemia. [Neural Res 1997; 19: 426-430]