Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat Article

Ferriero, DM, Sheldon, RA, Black, SM et al. (1995). Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat . 38(6), 912-918. 10.1203/00006450-199512000-00014

cited authors

  • Ferriero, DM; Sheldon, RA; Black, SM; Chuai, J

fiu authors

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. © 1995 International Pediatric Research Foundation, Inc.

publication date

  • January 1, 1995

Digital Object Identifier (DOI)

start page

  • 912

end page

  • 918

volume

  • 38

issue

  • 6