Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier

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dc.contributor.author Riachi, Naji J.
dc.contributor.author Dietrich, W. Dalton
dc.contributor.author Harik, Sami I.
dc.date.accessioned 2019-04-15T10:32:52Z
dc.date.available 2019-04-15T10:32:52Z
dc.date.copyright 1990 en_US
dc.date.issued 2019-04-15
dc.identifier.issn 1872-6240 en_US
dc.identifier.uri http://hdl.handle.net/10725/10436
dc.description.abstract Unlike primates, rats are resistant to systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, but direct infusion of MPTP into rat substantia nigra causes specific destruction of dopaminergic neurons. We now demonstrate that rats are resistant to MPTP neurotoxicity even when MPTP is injected directly into the brain circulation. Injection of 1–3.5 mg of MPTP into the internal carotid artery of Wistar rats causes no behavioral or motor abnormalities and small, but significant, dopamine loss in the ipsilateral striatum. MPTP caused no changes in the levels of norepinephrine or serotonin in the cerebral cortex. Higher doses of intracarotid MPTP were lethal. Pretreatment with pargyline, a monoamine oxidase inhibitor, did not alter the mortality but prevented dopamine depletion. The high uptake and retention of MPTP by rat brain, yet its failure to cause major dopaminergic toxicity suggest that MPTP is rapidly metabolized in brain capillaries to 1-methyl-4-phenylpyridinium (MPP+) and other polar metabolites that have difficulty in traversing the blood-brain barrier. Sequestration of MPTP metabolites in brain capillary endothelial cells could result in their dysfunction. However, we found no defects in the ability of the blood-brain barrier to prevent the entry of vascular aminoisobutyric acid or horseradish peroxidase into brain in spite of morphologic evidence of endothelial changes and astrocytic swelling after intracarotid MPTP injections. Our results provide further evidence that the rat's resistance to systemic MPTP neurotoxicity is probably due to its unique blood-brain barrier properties. en_US
dc.language.iso en en_US
dc.title Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 200902731 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Brain Research en_US
dc.journal.volume 533 en_US
dc.journal.issue 1 en_US
dc.article.pages 6-14 en_US
dc.keywords MPTP en_US
dc.keywords MPP en_US
dc.keywords Blood-brain barrier en_US
dc.keywords Rat resistance to MPTP toxicity en_US
dc.keywords Dopaminergic neurotoxicity en_US
dc.keywords Monoamine oxidase en_US
dc.identifier.doi https://doi.org/10.1016/0006-8993(90)91788-I en_US
dc.identifier.ctation Riachi, N. J., Dietrich, W. D., & Harik, S. I. (1990). Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier. Brain research, 533(1), 6-14. en_US
dc.author.email naji.riachi@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.sciencedirect.com/science/article/pii/000689939091788I en_US
dc.orcid.id https://orcid.org/0000-0002-8652-9698 en_US
dc.author.affiliation Lebanese American University en_US

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