Y. Hamada et al., INHIBITOR OF NITRIC-OXIDE SYNTHESIS REDUCES HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE NEONATAL RAT, Pediatric research, 35(1), 1994, pp. 10-14
We evaluated the neuroprotective effect of the nitric oxide synthesis
inhibitor, N(G)-nitro-L-arginine in a neonatal hypoxic-ischemic rat mo
del. Unilateral hypoxic-ischemic injury was produced in the brain of 7
-d-old rats using a combination of a common carotid artery ligation an
d a hypoxic (8% oxygen) exposure for 2.5 h. In our experimental condit
ion, 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 hypo
xia resulted in 77% reduction of the infarcted hemispheric volume and
87% reduction of the infarcted striatal volume compared to saline inje
cted controls. N(G)-nitro-L-arginine given 1.5 h before the insult als
o significantly prevented hypoxic-ischemic damage in the five hippocam
pal 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 nit
ric oxide plays a key role in producing neonatal hypoxic-ischemic brai
n damage.