Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke
Abstract Background Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1190-9 |
| _version_ | 1818311817038921728 |
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| author | Chen Chen Wei Jiang Zongjian Liu Fengwu Li Jian Yang Yanlong Zhao Yuanyuan Ran Yan Meng Xunming Ji Xiaokun Geng Huishan Du Xiaoming Hu |
| author_facet | Chen Chen Wei Jiang Zongjian Liu Fengwu Li Jian Yang Yanlong Zhao Yuanyuan Ran Yan Meng Xunming Ji Xiaokun Geng Huishan Du Xiaoming Hu |
| author_sort | Chen Chen |
| collection | DOAJ |
| description | Abstract Background Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke. Methods Noninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet. The blood and spleens were collected before and 1 h and 3 days after preconditioning to analyze the effect of RIPC on the spleen and the correlation between splenic and peripheral lymphocytes. Moreover, spleen weight and splenic lymphocytes were compared in stroke rats with or without RIPC. Finally, splenectomy was made 1 day or 2 weeks before RIPC and 90-min middle cerebral artery occlusion (MCAO). The infarct areas and deficits were assessed. Blood was collected 1 h after RIPC and 3 days after MCAO to explore the impact of splenectomy on RIPC-induced neuroprotection and immune changes. The contralateral and ipsilateral hemispheres were collected 3 days after MCAO to detect the infiltration of immune cells after RIPC and splenectomy. Results Flow cytometry analysis demonstrated that the RIPC promptly increased the percentages of CD3+CD8+ cytotoxic T (Tc) cells in the spleen with a relatively delayed elevation in CD3+CD161+ natural killer T (NKT) and CD3−CD45RA+ B lymphocytes. The percentages of circulating lymphocytes are positively correlated with the percentages of splenic lymphocytes in normal rats. Interestingly, RIPC resulted in negative correlations between the percentages of splenic and circulating T lymphocytes, while the correlation between splenic and circulating B lymphocytes remained positive. For animals subjected to RIPC followed by MCAO, RIPC increased splenic volume with an expansion of splenic lymphocytes 3 days after MCAO. Furthermore, the removal of the spleen 1 day or 2 weeks before RIPC and MCAO reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition. RIPC significantly reduced brain infiltration of Tc and NKT cells. Prior splenectomy showed no effect on immune cell infiltration after RIPC and stroke. Conclusion These results reveal an immunomodulatory effect of the spleen, effecting mainly the spleen-derived lymphocytes, during RIPC-afforded neuroprotection against cerebral ischemia. |
| first_indexed | 2024-12-13T08:07:59Z |
| format | Article |
| id | doaj.art-e0084088c5e54334a908ef1556835c9d |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T08:07:59Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj.art-e0084088c5e54334a908ef1556835c9d2022-12-21T23:54:16ZengBMCJournal of Neuroinflammation1742-20942018-05-0115111410.1186/s12974-018-1190-9Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against strokeChen Chen0Wei Jiang1Zongjian Liu2Fengwu Li3Jian Yang4Yanlong Zhao5Yuanyuan Ran6Yan Meng7Xunming Ji8Xiaokun Geng9Huishan Du10Xiaoming Hu11China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityDepartment of Pathology and Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityAbstract Background Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke. Methods Noninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet. The blood and spleens were collected before and 1 h and 3 days after preconditioning to analyze the effect of RIPC on the spleen and the correlation between splenic and peripheral lymphocytes. Moreover, spleen weight and splenic lymphocytes were compared in stroke rats with or without RIPC. Finally, splenectomy was made 1 day or 2 weeks before RIPC and 90-min middle cerebral artery occlusion (MCAO). The infarct areas and deficits were assessed. Blood was collected 1 h after RIPC and 3 days after MCAO to explore the impact of splenectomy on RIPC-induced neuroprotection and immune changes. The contralateral and ipsilateral hemispheres were collected 3 days after MCAO to detect the infiltration of immune cells after RIPC and splenectomy. Results Flow cytometry analysis demonstrated that the RIPC promptly increased the percentages of CD3+CD8+ cytotoxic T (Tc) cells in the spleen with a relatively delayed elevation in CD3+CD161+ natural killer T (NKT) and CD3−CD45RA+ B lymphocytes. The percentages of circulating lymphocytes are positively correlated with the percentages of splenic lymphocytes in normal rats. Interestingly, RIPC resulted in negative correlations between the percentages of splenic and circulating T lymphocytes, while the correlation between splenic and circulating B lymphocytes remained positive. For animals subjected to RIPC followed by MCAO, RIPC increased splenic volume with an expansion of splenic lymphocytes 3 days after MCAO. Furthermore, the removal of the spleen 1 day or 2 weeks before RIPC and MCAO reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition. RIPC significantly reduced brain infiltration of Tc and NKT cells. Prior splenectomy showed no effect on immune cell infiltration after RIPC and stroke. Conclusion These results reveal an immunomodulatory effect of the spleen, effecting mainly the spleen-derived lymphocytes, during RIPC-afforded neuroprotection against cerebral ischemia.http://link.springer.com/article/10.1186/s12974-018-1190-9Cerebral ischemiaSpleenLymphocytesLimb remote ischemic preconditioning |
| spellingShingle | Chen Chen Wei Jiang Zongjian Liu Fengwu Li Jian Yang Yanlong Zhao Yuanyuan Ran Yan Meng Xunming Ji Xiaokun Geng Huishan Du Xiaoming Hu Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke Journal of Neuroinflammation Cerebral ischemia Spleen Lymphocytes Limb remote ischemic preconditioning |
| title | Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke |
| title_full | Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke |
| title_fullStr | Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke |
| title_full_unstemmed | Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke |
| title_short | Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke |
| title_sort | splenic responses play an important role in remote ischemic preconditioning mediated neuroprotection against stroke |
| topic | Cerebral ischemia Spleen Lymphocytes Limb remote ischemic preconditioning |
| url | http://link.springer.com/article/10.1186/s12974-018-1190-9 |
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