Studies on the potential neurotoxic and convulsant effects of increased blood levels of quinolinic acid in rats with altered blood-brain barrier permeability

A. Vezzani, M. A. Stasi, H. Q. Wu, M. Castiglioni, B. Weckermann, R. Samanin

Research output: Contribution to journalArticle

Abstract

Intravenous injection of 450 mg/kg quinolinic acid (Quin), an endogenous kynurenine metabolite with excitotoxic properties, induced only minor electroencephalographic (EEG) modification and no neurotoxicity in rats with a mature blood-brain barrier (BBB). BBB permeability was altered in rats by focal unilateral irradiation of the cortex (7 mm in diameter and 5 mm in depth) with protons (60 Gy, 9 Gy/min). Three days after irradiation, Evans blue dye staining showed BBB breakdown in the dorsal hippocampus of the irradiated hemisphere. No neurotoxic or convulsant effects were observed as a consequence of the radiation itself. When BBB-lesioned rats were challenged with 225 mg/kg Quin iv, epileptiform activity was observed on EEG analysis. Tonic-clonic seizures were induced by 225-450 mg/kg Quin. Light microscopic analysis showed a dose-related excitotoxic type of lesion restricted to the hippocampus ipsilateral to the irradiated side. Neurodegeneration was prevented by local injection of 120 nmol d(-)2-amino-7-phosphonoheptanoic acid, a selective N-methyl-d-aspartate receptor antagonist. No lesions or EEG or behavioral modifications occurred after 450 mg/kg nicotinic acid, an inactive analog of Quin. The potential neurotoxic and convulsant effects of increased blood levels of Quin under conditions of altered BBB permeability are discussed.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalExperimental Neurology
Volume106
Issue number1
DOIs
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

Fingerprint Dive into the research topics of 'Studies on the potential neurotoxic and convulsant effects of increased blood levels of quinolinic acid in rats with altered blood-brain barrier permeability'. Together they form a unique fingerprint.

  • Cite this