Quinolinate-induced injury is enhanced in developing rat brain

William H. Trescher, John W. McDonald, Michael V. Johnston

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Quinolinate, a metabolite of tryptophan in the kynurenine pathway, has been hypothesized to play a role in neuronal injury through activation of the N-methyl-d-aspartate (NMDA) receptor. We evaluated the ontogeny and neuroprotective pharmacology of quinolinate-induced injury in the immature rat brain. Unilateral striatal microinjections of quinolinate (150 nmol/0.5 μl) were performed at seven ages between postnatal day (PND) 1 and 90. Injury was assessed by comparing the cross-sectional areas of the cerebral hemispheres ipsilateral and contralateral to the injection site in Nissl-stained coronal sections. The susceptibility to quinolinate-induced injury was enhanced in the immature brain with peak toxicity at PND 7 when the ipsilateral cerebral hemisphere was reduced by 16.1 ± 3.2%. In a dose-response comparison with NMDA-induced injury at PND 7, quinolinate injury was directly related to the dose injected (r2 = 0.73, P < 0.0001), but the neurotoxicity of quinolinate was 20-times less potent than NMDA. In the PND 7 rat brain, quinolinate-induced injury was completely blocked by MK-801 (1 mg/kg, i.p.) and CGS-19755 (10 mg/kg). Dextromethorphan (20 mg/kg) and dextrorphan (20 mg/kg) were partially protective. Ifenprodil, carbamazepine, and nifedipine did not significantly protect against quinolinate-induced injury. Finally, pretreatment with MK-801 (1 mg/kg) 24 h before intracerebral injection of quinolinate resulted in greater injury compared to controls. The findings indicate that quinolinate-induced injury is enhanced in the immature brain in a pattern that is similar to NMDA-induced injury.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalDevelopmental Brain Research
Volume83
Issue number2
DOIs
StatePublished - Dec 16 1994

All Science Journal Classification (ASJC) codes

  • Developmental Neuroscience
  • Developmental Biology

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