POTENTIATION OF N-METHYL-D-ASPARTATE MEDIATED BRAIN INJURY BY A HUMANIMMUNODEFICIENCY VIRUS-1 DERIVED PEPTIDE IN PERINATAL RODENTS

In this study, we tested the hypothesis that human immunodeficiency vi rus (HIV)-1-derived peptides augment the neurotoxicity of excitatory a mino acid agonists in vivo in postnatal day (PND) 7 rats. Stereotaxic intracerebral injections of the excitatory amino acid agonist N-methyl -D-aspartate (NMDA), alone or coinjected with an HIV-derived recombina nt fusion peptide envelope gag (env-gag) were performed in PND-7 rats [group I: 5 nmol NMDA, n = 20; group II: 5 nmol NMDA + low-dose (1 or 50 ng) env-gag, n = 27; group III: 5 nmol NMDA + high-dose (100 ng) en v-gag, n = 20], and brain injury was evaluated on PND 12. Based on his topathology scoring and measurements of hippocampal cross-sectional ar eas in the injected and contralateral hemispheres, coinjection of 100 ng of env-gag with 5 nmol of NMDA markedly increased the severity of r esulting injury (p < 0.002, comparing histopathology scores; p < 0.003 , comparing inter-hemispheric differences in hippocampal areas). These data suggest that in the developing nervous system HIV neurotoxicity may result, at least in part, from overactivation of excitatory amino acid receptors, and that perinatal rodent models may provide clinicall y relevant insights about the pathophysiology of HIV-mediated brain in jury.