NITRIC-OXIDE INHIBITORS ATTENUATE ISCHEMIC DEGENERATION IN THE CA1 REGION OF RAT HIPPOCAMPAL SLICES

We examined the involvement of nitric oxide (NO) in ischemic brain dam age using hippocampal slices prepared from 30 day old albino rats and exposed to 20 min of oxygen/glucose deprivation (ischemia) followed by 90 min postincubation in oxygen- and glucose-containing media. Damage in the CA1 region was rated on a 0 (intact) to 4 (severe neuronal dam age) scale by a rater blind to the experimental condition. Control sli ces exposed to ischemia were rated as 2.8 +/- 0.4 (N = 12). L-N-G-Mono methylarginine (100 mu M) and L-N-G-nitroarginine (100 mu M), non-sele ctive NO synthase (NOS) inhibitors, diminished ischemic damage (0.6 +/ - 0.3, N = 8, and 1.0 +/- 0.5, N = 4, respectively). An inhibitor of b rain NOS, 7-nitroindazole (30 mu M), was also effective against ischem ic degeneration (0.7 +/- 0.3, N = 5). These results suggest that activ ation of NOS is involved in ischemic degeneration in the CA1 region.