Abstract
ABSTRACT: The vulnerability of the developing CNS to hypoxia-ischemia (H-I) differs from that of the mature brain and is due in part to release of nitric oxide (NO) from parenchymal neurons. If NO is important in the generation of excitotoxic injury after H-I in the developing CNS, then selective destruction of the neuronal nitric oxide synthase (nNOS) cells before H-I should lessen the injury seen after the insult. Using low dose quisqualic acid (QA) injected into neonatal (postnatal d 7) parietal cortex, the nNOS neurons were eliminated while sparing other neuronal and glial populations as ascertained by NADPH diaphorase histochemistry, nNOS immunocytochemistry, and Nissl counterstain. Animals subjected to focal ischemia followed by global hypoxia 24 h after the intracortical injection of QA had more viable cortex remaining than vehicle-injected animals (83.4 ± 4.3% versus 62.7 ± 8.3%) and lower injury severity represented by less neuronal loss and gliosis. Intracortical injections of QA without H-I resulted in minimal cell loss at the injection site with elimination of nNOS neurons throughout the parietal cortex. Microglial and astrocytic proliferation was seen in areas damaged by H-I 3 wk after injury and clearly marked infarcted areas. Prevention or elimination of NO production from nNOS cells can prevent much of the delayed neuronal necrosis seen after H-I in the developing CNS.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ferriero, D., Sheldon, R., Black, S. et al. Selective Destruction of Nitric Oxide Synthase Neurons with Quisqualate Reduces Damage after Hypoxia-Ischemia in the Neonatal Rat. Pediatr Res 38, 912–918 (1995). https://doi.org/10.1203/00006450-199512000-00014
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199512000-00014
This article is cited by
-
Free radicals and neonatal encephalopathy: mechanisms of injury, biomarkers, and antioxidant treatment perspectives
Pediatric Research (2020)
-
Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia–ischemia
Pediatric Research (2013)
-
Pathological apoptosis in the developing brain
Apoptosis (2007)