Potentiation of N-methyl-D-aspartate-mediated brain injury by a human immunodeficiency virus-1-derived peptide in perinatal rodents.
In this study, we tested the hypothesis that human immunodeficiency virus (HIV)-1-derived peptides augment the neurotoxicity of excitatory amino 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 recombinant 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) env-gag, n = 20], and brain injury was evaluated on PND 12. Based on histopathology scoring and measurements of hippocampal cross-sectional areas in the injected and contralateral hemispheres, coinjection of 100 ng of env-gag with 5 nmol of NMDA markedly increased the severity of resulting injury (p < 0.002, comparing histopathology scores; p < 0.003, comparing interhemispheric 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 clinically relevant insights about the pathophysiology of HIV-mediated brain injury.
Barks
J D
JD
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Nair
M P
MP
Schwartz
S A
SA
Silverstein
F S
FS
D015526:AIDS Dementia Complex / Q000209:etiology; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000633:toxicity*; D015683:Gene Products, gag / Q000633:toxicity*; D015497:HIV-1 / Q000472:pathogenicity*; D006624:Hippocampus / Q000293:injuries / Q000473:pathology; D016202:N-Methylaspartate / Q000633:toxicity*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000633:toxicity
D015686:Gene Products, env; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D016202:N-Methylaspartate