Abstract 6

In the rat striatum, the enzyme nitric oxide synthase (NOS) is present in a dense fiber network and in few medium sized non-spinal interneurons. This enzyme is activated by glutamate throughout the influx of Ca2+ to the cell. A sustained activation of NOS caused by excessive release of glutamate, results in strongly increased NO that is a potent activator of the soluble guanylyl cyclase resulting in the synthesis of intracellular cGMP. Previous work showed that NO-containing striatal neurons suffer short-and long-term changes after perinatal asphyctic insult and that changes were prevented by hypothermic exposure. In order to know if this morphological changes were due to an excess of the NOS activity we designed the measurements of striatal cGMP levels, with the aim to evaluate NOS activity in asphyctic and hypothermic treated pups using a model of severe perinatal (SPA). The levels of striatal cGMP of normal pups (PN10) using a RIA procedure were compared to those subjected to SPA and SPA treated with hypothermia during or after insult. cGMP levels in striatal tissue from control pups (PN10) were 25.8 pmol/mg protein and in the SPA group 38.1 pmol/mg which is an increase of approx 70% (p<0.01). Hypothermia during as well as after insult was capable to prevent this increase of cGMP. L-NAME at 0.1 mM decreased cGMP levels in control, SPA and hypothermic treated pups without differences between them. Nitroprusside stimulated cGMP showed no differences between groups. These findings indicate that high cGMP levels in the striatum of rats subjected to SPA are under control of an hyperactive NOS leading to excessive NO production which could be harmful to the cerebral tissue. Hypothermia may prove a useful therapeutic agent against cerebral oxidative stress as it reduces NOS activity.