Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice
Neural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic te...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/4364302 |
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| author | Yifan Lu Lu Jiang Wanlu Li Meijie Qu Yaying Song Xiaosong He Zhijun Zhang Guo-Yuan Yang Yongting Wang |
| author_facet | Yifan Lu Lu Jiang Wanlu Li Meijie Qu Yaying Song Xiaosong He Zhijun Zhang Guo-Yuan Yang Yongting Wang |
| author_sort | Yifan Lu |
| collection | DOAJ |
| description | Neural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic techniques to control the activity of striatal neurons and investigated how their activity affected the survival and migration of transplanted NSCs and overall neurological outcome after ischemic stroke. NSCs cultured from transgenic mice expressing fluorescent protein were transplanted into the peri-infarct region of the striatum after transient middle cerebral artery occlusion (tMCAO) surgery. The striatal neurons were excited or inhibited for 15 minutes daily via implanted optical fiber after tMCAO. The results revealed that mice which received NSC transplantation and optogenetic inhibition had smaller brain infarct volume and increased NSC migration compared to the NSC alone or PBS group (p<0.05). In contrast, mice which received NSC transplantation and optogenetic excitation showed no difference in infarct volume and neurological behavior improvement compared to the PBS control group. In vitro experiments further revealed that the conditioned media from excited GABAergic neurons reduced NSC viability through paracrine mechanisms. Conclusion. Optogenetic inhibition of striatal neuronal activity further improved neurological recovery after NSC transplantation at the subacute phase after brain ischemia. |
| format | Article |
| id | doaj-art-997286c08c6e4dd286fd144d1f527cfe |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-997286c08c6e4dd286fd144d1f527cfe2025-02-03T01:20:30ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/43643024364302Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in MiceYifan Lu0Lu Jiang1Wanlu Li2Meijie Qu3Yaying Song4Xiaosong He5Zhijun Zhang6Guo-Yuan Yang7Yongting Wang8Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Human Anatomy, Guangzhou Medical University, Guangzhou 510182, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaNeural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic techniques to control the activity of striatal neurons and investigated how their activity affected the survival and migration of transplanted NSCs and overall neurological outcome after ischemic stroke. NSCs cultured from transgenic mice expressing fluorescent protein were transplanted into the peri-infarct region of the striatum after transient middle cerebral artery occlusion (tMCAO) surgery. The striatal neurons were excited or inhibited for 15 minutes daily via implanted optical fiber after tMCAO. The results revealed that mice which received NSC transplantation and optogenetic inhibition had smaller brain infarct volume and increased NSC migration compared to the NSC alone or PBS group (p<0.05). In contrast, mice which received NSC transplantation and optogenetic excitation showed no difference in infarct volume and neurological behavior improvement compared to the PBS control group. In vitro experiments further revealed that the conditioned media from excited GABAergic neurons reduced NSC viability through paracrine mechanisms. Conclusion. Optogenetic inhibition of striatal neuronal activity further improved neurological recovery after NSC transplantation at the subacute phase after brain ischemia.http://dx.doi.org/10.1155/2017/4364302 |
| spellingShingle | Yifan Lu Lu Jiang Wanlu Li Meijie Qu Yaying Song Xiaosong He Zhijun Zhang Guo-Yuan Yang Yongting Wang Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice Stem Cells International |
| title | Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice |
| title_full | Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice |
| title_fullStr | Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice |
| title_full_unstemmed | Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice |
| title_short | Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice |
| title_sort | optogenetic inhibition of striatal neuronal activity improves the survival of transplanted neural stem cells and neurological outcomes after ischemic stroke in mice |
| url | http://dx.doi.org/10.1155/2017/4364302 |
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