ABSTRACI'. We evaluated the neuroprotective effect of lium in the conversion of L-arginine to L-citrulline by the enzyme the nitric oxide synthesis inhibitor, NC-nitro-L-arginine in NO synthase ( 9 , whose activity has also been reported in forea neonatal hypoxic-ischemic rat model. Unilateral hypoxic-brain homogenates (6). NMDA stimulates NO synthesis (7), and ischemic iqjury was produced in the brain of 7-dsld rats NO mediates glutamate neurotoxicity in vitro (8). NOARG, an using a combition of a common carotid artery ligation analog of L-arginine, competitively inhibits the enzymatic forand a hypoxic (8% oxygen) exposure for 2.5 h. In our mation of NO both in cultured endothelial cells (9) and cerebellar experimental condition, rectal temperatures did not differ homogenates (lo), also prevents neurotoxicity induced by between NC-nitro-L-argininetreated and salineinjected NMDA in cortical cultures (8), and easily crosses the blood-brain pups. We killed the animals 72 h later and assessed the barrier (10).
hypoxic-ischemic brain damage histologically. NG-nitro-L-Contradictory reports concerning the possible neuroprotective 9 nine (2 mg/kg) administered intraperitoneally 1.5 h effect of NO synthesis inhibitors in adult models (1 1-16) be ore hypoxia resulted in 77% reduction of the infarcted prompted us to investigate whether NO was related to the genesis hemispheric volume and 87% reduction of the infarcted of cerebral hypoxic-ischemic brain damage in neonates. Sevenstriatal volume compared to saline injected controls. P -d-old rats were subjected to unilateral carotid artery ligation nitro-L-arginine given 1.5 h before the insult also signifi-followed by hypoxic exposure. This neonatal rat model shows cantly prevented hypoxic-ischemic damage in the five hip-infarction of the cerebral hemisphere ipsilateral to the carotid pocrunpal structures examined, dentate gyruq CA4, CA3, artery ligation (17), and has been frequently used to investigate CAI, and subiculum. NG-nitro-L-arginine administered im-the pathogenesis of cerebral hypoxia ischemia (for review see mediately after hypoxia did not prevent hypoxic-ischemic Refs. 1 and 18). We investigated the neuroprotective effect of brain damage. These results indicate that nitric oxide plays NOARG administered before and after a hypoxic insult. a key role in producing neonatal hypoxic-ischemic brain damage. (Pediatr RPS 35: 10-14,1994)
MATERIALS AND METHODS
AbbreviationsWe used the method of Rice et al. (17) to produce hypoxicischemic brain damage in neonatal rats. On the day of surgery, NMDA, N-methyl-aspa art ate 7-d-old Std:Wister rat (Japan SLC, Inc.) littermates (the day of NO, nitric oxide birth is defined as d 1) were paired according to sex and body NOARC, NC-nitro-L-arginine weight (f0.5 g), each pair consisting of a pup assigned to NOARG treatment and a saline-injected control. If one member of a pair died, the other member was discarded. Under ether anesthesia, the left carotid artery was exposed through a midline neck incision, doubly ligated, and severed b...
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