Studies on the potential neurotoxic and convulsant effects of increased blood levels of quinolinic acid in rats with altered blood-brain barrier permeability
| Autor: | B. Weckermann, M. Castiglioni, Annamaria Vezzani, M.A. Stasi, Hui-qiu Wu, Rosario Samanin |
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| Rok vydání: | 1989 |
| Předmět: |
Male
medicine.medical_specialty Pyridines medicine.drug_class Motor Activity Blood–brain barrier Hippocampus Lesion chemistry.chemical_compound Developmental Neuroscience Seizures Internal medicine medicine Animals Amino Acids Evans Blue Cerebral Cortex Chemistry Neurotoxicity Electroencephalography Rats Inbred Strains Quinolinic Acid medicine.disease Receptor antagonist Rats Quinolinic Acids Endocrinology medicine.anatomical_structure 2-Amino-5-phosphonovalerate Neurology Biochemistry Blood-Brain Barrier Convulsant Anticonvulsants Nervous System Diseases Protons medicine.symptom Kynurenine Quinolinic acid |
| Zdroj: | Experimental Neurology. 106:90-98 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/0014-4886(89)90149-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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