Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion
Purpose. Drug delivery by transferrin receptor-mediated transport at the blood-brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse mod...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-09-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19576 |
| _version_ | 1797759924810285056 |
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| author | Jiukuan Hao Ulrich Bickel |
| author_facet | Jiukuan Hao Ulrich Bickel |
| author_sort | Jiukuan Hao |
| collection | DOAJ |
| description | Purpose. Drug delivery by transferrin receptor-mediated transport at the blood-brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse model of brain focal ischemia, permanent or transient middle cerebral artery occlusion (MCAO). Methods. Brain accumulation of 125I-labeled 8D3, a mouse-specific transferrin receptor antibody, or of the isotype control UPC-10 used as vascular marker, was measured autoradiographically by phosphorimaging in the core ischemic region on cryostat brain sections up to 24h after ischemia or reperfusion. Cerebral blood flow was quantitatively determined in the same animals after administration of 99mTc-ECD (Neurolite). Results. Apparent volume of distribution obtained with UPC-10 indicated no significant nonspecific leakage of the blood-brain barrier at any time point. Although brain uptake of 8D3 gradually declined compared to healthy tissue under MCAO, VD remained significantly higher than VD of UPC-10 up to 5h. In transient MCAO the brain uptake recovered to levels as in healthy tissue immediately after reperfusion. Conclusion. Transferrin receptor-mediated brain uptake, which is an energy dependent vesicular transport process, is sensitive to reduction in blood supply but remains partially functional for several hours after onset of ischemia. The uptake shows complete recovery after reperfusion. These results support the use of transferrin receptor-mediated brain drug delivery in the early phase of ischemia and in the phase when blood flow is restored.
This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page. |
| first_indexed | 2024-03-12T18:51:27Z |
| format | Article |
| id | doaj.art-4559ee2973a7439595f93f41791cc124 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2024-03-12T18:51:27Z |
| publishDate | 2013-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-4559ee2973a7439595f93f41791cc1242023-08-02T07:11:48ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262013-09-0116410.18433/J3B303Transferrin Receptor Mediated Brain Uptake During Ischemia and ReperfusionJiukuan Hao0Ulrich Bickel1Department of Pharmaceutical Sciences, University of CincinnatiDepartment of Pharmaceutical Sciences and Center for Blood-Brain Barrier Research, Texas Tech University Health Sciences CenterPurpose. Drug delivery by transferrin receptor-mediated transport at the blood-brain barrier has shown beneficial effects in animal models of stroke, but it is unclear whether receptor mediated uptake remains functional in the ischemic tissue. The present study addressed that question in a mouse model of brain focal ischemia, permanent or transient middle cerebral artery occlusion (MCAO). Methods. Brain accumulation of 125I-labeled 8D3, a mouse-specific transferrin receptor antibody, or of the isotype control UPC-10 used as vascular marker, was measured autoradiographically by phosphorimaging in the core ischemic region on cryostat brain sections up to 24h after ischemia or reperfusion. Cerebral blood flow was quantitatively determined in the same animals after administration of 99mTc-ECD (Neurolite). Results. Apparent volume of distribution obtained with UPC-10 indicated no significant nonspecific leakage of the blood-brain barrier at any time point. Although brain uptake of 8D3 gradually declined compared to healthy tissue under MCAO, VD remained significantly higher than VD of UPC-10 up to 5h. In transient MCAO the brain uptake recovered to levels as in healthy tissue immediately after reperfusion. Conclusion. Transferrin receptor-mediated brain uptake, which is an energy dependent vesicular transport process, is sensitive to reduction in blood supply but remains partially functional for several hours after onset of ischemia. The uptake shows complete recovery after reperfusion. These results support the use of transferrin receptor-mediated brain drug delivery in the early phase of ischemia and in the phase when blood flow is restored. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19576 |
| spellingShingle | Jiukuan Hao Ulrich Bickel Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion Journal of Pharmacy & Pharmaceutical Sciences |
| title | Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion |
| title_full | Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion |
| title_fullStr | Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion |
| title_full_unstemmed | Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion |
| title_short | Transferrin Receptor Mediated Brain Uptake During Ischemia and Reperfusion |
| title_sort | transferrin receptor mediated brain uptake during ischemia and reperfusion |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19576 |
| work_keys_str_mv | AT jiukuanhao transferrinreceptormediatedbrainuptakeduringischemiaandreperfusion AT ulrichbickel transferrinreceptormediatedbrainuptakeduringischemiaandreperfusion |