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

Journal Article · Sun Oct 01 00:00:00 EDT 1989 · Experimental Neurology; (USA)

DOI:https://doi.org/10.1016/0014-4886(89)90149-0· OSTI ID:5224283

Vezzani, A; Stasi, M A; Wu, H Q; Castiglioni, M; Weckermann, B; Samanin, R ^[1]

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1. Istituto di Ricerche Farmacologiche Mario Negri, Milano (Italy)

Intravenous injection of 450 mg/kg quinolinic acid (Quin), an endogenous kynurenine metabolite with excitotoxic properties, induced only minor electroencephalographic (EEG) modifications 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. Neuro-degeneration 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.

• OSTI ID: 5224283
• Journal Information: Experimental Neurology; (USA), Vol. 106:1; ISSN 0014-4886
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTICONVULSANTS
BIOLOGICAL EFFECTS
BLOOD-BRAIN BARRIER
PERMEABILITY
AMINO ACIDS
CEREBRAL CORTEX
DOSE-RESPONSE RELATIONSHIPS
ELECTROENCEPHALOGRAPHY
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CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CEREBRUM
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
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RODENTS
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560152* - Radiation Effects on Animals- Animals