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 damage 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 damage) scale by a rater blind to the experimental condition. Control slices exposed to ischemia were rated as 2.8 +/- 0.4 (N = 12). L-NG-Monomethylarginine (100 microM) and L-NG-nitroarginine (100 microM), non-selective NO synthase (NOS) inhibitors, diminished ischemic damage (0.6 +/- 0.3, N = 8, and 1.0 +/- 0.5, N = 4, respectively). An inhibitor of brain NOS, 7-nitroindazole (30 microM), was also effective against ischemic degeneration (0.7 +/- 0.3, N = 5). These results suggest that activation of NOS is involved in ischemic degeneration in the CA1 region.