Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen: role of NOS activation

Nitric oxide is involved in the mechanism of hyperbaric oxygen (HBO2) brain toxicity as nitric oxide synthase (NOS) inhibitors delay latent time before the onset of seizures. The purpose of this study was to investigate if seizures affect sensitivity to convulsions during subsequent exposure to HBO2 and to determine if NOS activity and expression is changed after HBO2 seizures. Rats were exposed to 5 atm (gauge pressure) 100% O-2 until seizures recorded by electroencephalograph (EEG) and reexposed 1, 2, or 6 days later. Latency to seizures was significantly shorter (P<0.05) in animals reexposed 1 or 2 days after the first exposure. Activity of calcium-dependent NOS activity in cortex was significantly higher 1 and 2 days after seizures compared with controls (P<0.05), while calcium-independent NOS activity was not changed during the 6-day post-seizure interval. The expression of neuronal NOS (nNOS) protein determined by Western blot was higher 1 and 2 days after seizures (P<0.05), while the expression of endothelial (eNOS) and inducible (iNOS) remained unchanged. nNOS upregulation 1 and 2 days after seizures and protection against HBO2 seizures by nNOS-specific inhibitor 7-nitroindazole (7-NI) suggest possible involvement of NO in the mechanism of increased sensitivity to HBO2 in reexposures. (C) 2001 Published by Elsevier Science B.V.