title: Excitotoxic brain injury suppresses striatal high-affinity glutamate uptake in perinatal rats.
abstract: In immature rodent brain, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) is a potent neurotoxin. In postnatal day (PND)-7 rats, intrastriatal injection of 25 nmol of NMDA results in extensive ipsilateral forebrain injury. In this study, we examined alterations in high-affinity [3H]glutamate uptake (HAGU) in NMDA-lesioned striatum. HAGU was assayed in synaptosomes, prepared from lesioned striatum, the corresponding contralateral striatum, or unlesioned controls. Twenty-four hours after NMDA injection (25 nmol), HAGU declined 44 +/- 8% in lesioned tissue, compared with the contralateral striatum (mean +/- SEM, n = 6 assays, p less than 0.006, paired t test). Doses of 5-25 nmol of NMDA resulted in increasing suppression of HAGU (5 nmol, n = 3; 12.5 nmol, n = 3; and 25 nmol, n = 5 assays; p less than 0.01, regression analysis). The temporal evolution of HAGU suppression was biphasic. There was an early transient suppression of HAGU (-28 +/- 4% at 1 h; p less than 0.03, analysis of variance, comparing changes at 0.5, 1, 2, and 3 h after lesioning); 1 or 5 days postinjury there was sustained loss of HAGU (at 5 days, -56 +/- 11%, n = 3, p less than 0.03, paired t test, lesioned versus contralateral striata).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor 48109-0570.
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.forename: J W
authors.initials: JW
authors.lastname: McDonald
authors.forename: M V
authors.initials: MV
authors.lastname: Johnston
authors.forename: F S
authors.initials: FS
authors.lastname: Silverstein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
chemical_list: D005971:Glutamates; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate