Early neuroprotective effect of nitric oxide in developing rat brain irradiated in utero

Pregnant Wistar rats were exposed on day 17 of gestation to 1 Gy gamma irradiation from a Co(60) source. Even though it is established that gamma radiation-dependent damage is mainly due to free radical generation neither the ascorbyl radical/ascorbate ratio nor the lipid radical content in developing rat brain were affected by prenatal irradiation. A distinctive EPR signal for the adduct NO-Fe-MGD (g=2.03 and a(N)=12.5 G) was detected in brain homogenates prepared from irradiated rats. Nitric oxide (NO)-dependent EPR signal increased in a time-dependent manner up to 2h post-irradiation. NO concentration in unirradiated brains was 37+/-4 pmol/g brain and 45+/-2, 77+/-5 and 216+/-6 after 30, 60 and 120 min post-irradiation, respectively. Total nitric oxide synthase activity was increased by 77 and 51% after 30 and 60 min post-irradiation, respectively, and returned to control values after 120 min. Thus, increased NO steady-state concentration could be ascribed to an increase in NOS activity. Taken as a whole, these results suggest that NO might act to protect the developing brain from the cytotoxicity of reactive species.