Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier
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 MPT...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , |
| التنسيق: | article |
| منشور في: |
1990
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/10436 https://doi.org/10.1016/0006-8993(90)91788-I http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/000689939091788I |
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| _version_ | 1864513467444101120 |
|---|---|
| author | Riachi, Naji J. |
| author2 | Dietrich, W. Dalton Harik, Sami I. |
| author2_role | author author |
| author_facet | Riachi, Naji J. Dietrich, W. Dalton Harik, Sami I. |
| author_role | author |
| dc.creator.none.fl_str_mv | Riachi, Naji J. Dietrich, W. Dalton Harik, Sami I. |
| dc.date.none.fl_str_mv | 1990 2019-04-15T10:32:52Z 2019-04-15T10:32:52Z 2019-04-15 |
| dc.identifier.none.fl_str_mv | 1872-6240 http://hdl.handle.net/10725/10436 https://doi.org/10.1016/0006-8993(90)91788-I 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/000689939091788I |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Brain Research |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_73501cb63d6b54373de99f38ce8eac8b |
| identifier_str_mv | 1872-6240 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/10436 |
| publishDate | 1990 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrierRiachi, Naji J.Dietrich, W. DaltonHarik, Sami I.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.PublishedN/A2019-04-15T10:32:52Z2019-04-15T10:32:52Z19902019-04-15Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1872-6240http://hdl.handle.net/10725/10436https://doi.org/10.1016/0006-8993(90)91788-IRiachi, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.sciencedirect.com/science/article/pii/000689939091788IenBrain Researchinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/104362021-03-19T10:45:32Z |
| spellingShingle | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier Riachi, Naji J. |
| status_str | publishedVersion |
| title | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| title_full | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| title_fullStr | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| title_full_unstemmed | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| title_short | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| title_sort | Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier |
| url | http://hdl.handle.net/10725/10436 https://doi.org/10.1016/0006-8993(90)91788-I http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/000689939091788I |