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

Related Subjects

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