Excitotoxic Brain Injury Suppresses Striatal High‐Affinity Glutamate Uptake in Perinatal Rats

Bernadine Hu, John W. McDonald, Michael V. Johnston, Faye S. Silverstein

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16 Scopus citations


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 < 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 < 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 < 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 < 0.03, paired t test, lesioned versus contralateral striata). Treatment with the noncompetitive NMDA antagonist MK‐801 (1 mg/kg i.p.) attenuated both the early and subsequent irreversible suppression of HAGU (1 h postlesion −28 ± 4%, n = 6 assays versus −12.6 ± 5% with MK‐801, n = 4, p= 0.005; 24 h postlesion, −44 ± 8%, n = 5, versus +2.4 ± 6%, n = 3 with MK‐801, p= 0.01, Wilcoxon ranked sum tests). In immature brain excitotoxic lesions produce an acute reversible suppression of HAGU, and a delayed long‐lasting reduction in HAGU secondary to brain injury. These data suggest that accumulation of endogenous glutamate, as a consequence of the acute disruption of HAGU, could contribute to the pathogenesis of excitotoxic neuronal injury.

Original languageEnglish (US)
Pages (from-to)933-937
Number of pages5
JournalJournal of Neurochemistry
Issue number3
StatePublished - Mar 1991
Externally publishedYes


  • Glutamate
  • Injury
  • N‐Methyl‐D‐aspartate
  • Perinatal
  • Striatum
  • Uptake

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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