INHIBITOR OF NITRIC-OXIDE SYNTHESIS REDUCES HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE NEONATAL RAT

We evaluated the neuroprotective effect of the nitric oxide synthesis inhibitor, N(G)-nitro-L-arginine in a neonatal hypoxic-ischemic rat model. Unilateral hypoxic-ischemic injury was produced in the brain of 7-d-old rats using a combination of a common carotid artery ligation and a hypoxic (8% oxygen) exposure for 2.5 h. In our experimental condition, rectal temperatures did not differ between N(G)-nitro-L-arginine-treated and saline-injected pups. We killed the animals 72 h later and assessed the hypoxic-ischemic brain damage histologically. N(G)-nitro-L-arginine (2 mg/kg) administered intraperitoneally 1.5 h before hypoxia resulted in 77% reduction of the infarcted hemispheric volume and 87% reduction of the infarcted striatal volume compared to saline injected controls. N(G)-nitro-L-arginine given 1.5 h before the insult also significantly prevented hypoxic-ischemic damage in the five hippocampal structures examined, dentate gyrus, CA4, CA3, CA1, and subiculum. N(G)-nitro-L-arginine administered im mediately after hypoxia did not prevent hypoxic-ischemic brain damage. These results indicate that nitric oxide plays a key role in producing neonatal hypoxic-ischemic brain damage.