Increased nitric oxide synthesis is not involved in delayed cerebral energy failure following focal hypoxic-ischemic injury to the developing brain

This study addressed the hypothesis that the delayed impairment in cerebral energy metabolism that develops 10-24 h after transient hypoxia-ischemia i n the developing brain is mediated by induction of increased nitric oxide s ynthesis. Four groups of 14-d-old Wistar rat pups were studied. Group 1 was subjected to unilateral carotid artery ligation and hypoxia followed immed iately by treatment with the nitric oxide synthase (NOS) inhibitor, N-omega -nitro-L-arginine methyl ester (L-NAME, 30 mg/kg). Group 2 underwent hypoxi a-ischemia but received saline vehicle. Group 3 received L-NAME without hyp oxia-ischemia, and group 4, saline vehicle alone. At defined times after in sult, the expression of neuronal and inducible NOS were determined and calc ium-dependent and -independent NOS activities measured. Cerebral energy met abolism was observed using P-31 magnetic resonance spectroscopy. At 48 h af ter insult, the expression of inducible NOS increased, whereas neuronal NOS at 24 h decreased on the infarcted side. Calcium-dependent NOS activity wa s higher than calcium-independent NOS activity, but did not increase within 36 h after insult, and was significantly inhibited by the administration o f L-NAME. However, L-NAME did not prevent delayed impairment of cerebral en ergy metabolism or ameliorate infarct size. These results suggest that the delayed decline in cerebral energy metabolism after hypoxia-ischemia in the 14-d-old rat brain is not mediated by increased nitric oxide synthesis.