Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents
To date, few studies have systematically evaluated the most appropriate location for grafting catechoiaminergic cells as a potential treatment for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
1996-09-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/096368979600500508 |
| _version_ | 1818323160976588800 |
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| author | Dwaine F. Emerich Shelley R. Winn Mark D. Lindner |
| author_facet | Dwaine F. Emerich Shelley R. Winn Mark D. Lindner |
| author_sort | Dwaine F. Emerich |
| collection | DOAJ |
| description | To date, few studies have systematically evaluated the most appropriate location for grafting catechoiaminergic cells as a potential treatment for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the lateral ventricle of 6-OHDA–treated rats is as effective as intrastriatal implants on reducing apomorphine-induced rotational behavior, and 2) to determine if the survival of encapsulated PC12 cells is differentially affected by the implant site. Polymer-encapsulated PC12 cells were implanted into either the striatum or lateral ventricle of unilateral 6-OHDA–lesioned rats. Animals were tested for apomorphine-induced rotations over a 6-wk period. Only those animals that received intrastriatal implants of encapsulated PC12 cells showed a reduction in rotation behavior. Moreover, removal of the devices from the striatum resulted in a return to preimplant rotation levels. Postexplant neurochemical analyses demonstrated that the potassium-evoked l-dopa device output increased in vivo while the potassium-evoked dopamine output from the devices decreased over time in vivo. The location of the implant significantly affected catecholamine output from the PC12 cell-loaded devices. The increase in potassium-evoked l-dopa output was greatest, as was the decrease in potassium-evoked dopamine output, from those devices implanted in the striatum. Basal output of dopamine and DOPAC was also significantly higher from devices explanted from the lateral ventricle. These results demonstrate that the continued presence of intrastriatal implants of encapsulated PC12 cells is required to maintain the behavioral effects in 6-OHDA–lesioned rats. In addition, the site of implantation appears to affect device output. These results provide additional support for intraparenchymal delivery of l-dopa and dopamine via polymer encapsulation as a possible treatment for PD. |
| first_indexed | 2024-12-13T11:08:17Z |
| format | Article |
| id | doaj.art-aed3786d481d4690ac94f94b96f5beb2 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T11:08:17Z |
| publishDate | 1996-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-aed3786d481d4690ac94f94b96f5beb22022-12-21T23:48:54ZengSAGE PublishingCell Transplantation0963-68971555-38921996-09-01510.1177/096368979600500508Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian RodentsDwaine F. Emerich0Shelley R. Winn1Mark D. Lindner2CytoTherapeutics, Inc., 2 Richmond Square, Providence, RI 02906, USACytoTherapeutics, Inc., 2 Richmond Square, Providence, RI 02906, USACytoTherapeutics, Inc., 2 Richmond Square, Providence, RI 02906, USATo date, few studies have systematically evaluated the most appropriate location for grafting catechoiaminergic cells as a potential treatment for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the lateral ventricle of 6-OHDA–treated rats is as effective as intrastriatal implants on reducing apomorphine-induced rotational behavior, and 2) to determine if the survival of encapsulated PC12 cells is differentially affected by the implant site. Polymer-encapsulated PC12 cells were implanted into either the striatum or lateral ventricle of unilateral 6-OHDA–lesioned rats. Animals were tested for apomorphine-induced rotations over a 6-wk period. Only those animals that received intrastriatal implants of encapsulated PC12 cells showed a reduction in rotation behavior. Moreover, removal of the devices from the striatum resulted in a return to preimplant rotation levels. Postexplant neurochemical analyses demonstrated that the potassium-evoked l-dopa device output increased in vivo while the potassium-evoked dopamine output from the devices decreased over time in vivo. The location of the implant significantly affected catecholamine output from the PC12 cell-loaded devices. The increase in potassium-evoked l-dopa output was greatest, as was the decrease in potassium-evoked dopamine output, from those devices implanted in the striatum. Basal output of dopamine and DOPAC was also significantly higher from devices explanted from the lateral ventricle. These results demonstrate that the continued presence of intrastriatal implants of encapsulated PC12 cells is required to maintain the behavioral effects in 6-OHDA–lesioned rats. In addition, the site of implantation appears to affect device output. These results provide additional support for intraparenchymal delivery of l-dopa and dopamine via polymer encapsulation as a possible treatment for PD.https://doi.org/10.1177/096368979600500508 |
| spellingShingle | Dwaine F. Emerich Shelley R. Winn Mark D. Lindner Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents Cell Transplantation |
| title | Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents |
| title_full | Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents |
| title_fullStr | Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents |
| title_full_unstemmed | Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents |
| title_short | Continued Presence of Intrastriatal but not Intraventricular Polymer-Encapsulated PC12 Cells is Required for Alleviation of Behavioral Deficits in Parkinsonian Rodents |
| title_sort | continued presence of intrastriatal but not intraventricular polymer encapsulated pc12 cells is required for alleviation of behavioral deficits in parkinsonian rodents |
| url | https://doi.org/10.1177/096368979600500508 |
| work_keys_str_mv | AT dwainefemerich continuedpresenceofintrastriatalbutnotintraventricularpolymerencapsulatedpc12cellsisrequiredforalleviationofbehavioraldeficitsinparkinsonianrodents AT shelleyrwinn continuedpresenceofintrastriatalbutnotintraventricularpolymerencapsulatedpc12cellsisrequiredforalleviationofbehavioraldeficitsinparkinsonianrodents AT markdlindner continuedpresenceofintrastriatalbutnotintraventricularpolymerencapsulatedpc12cellsisrequiredforalleviationofbehavioraldeficitsinparkinsonianrodents |