Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway
Abstract Background Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia‐reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg...
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| Format: | Article |
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Wiley
2023-06-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.3030 |
| _version_ | 1797802412889604096 |
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| author | Yuan Shan Le Wang Jingying Sun Sha Chang Wei Di Hua Lv |
| author_facet | Yuan Shan Le Wang Jingying Sun Sha Chang Wei Di Hua Lv |
| author_sort | Yuan Shan |
| collection | DOAJ |
| description | Abstract Background Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia‐reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti‐inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)‐induced model. Results Fifty rats were randomly allocated into five groups, including the sham group (n = 10), EP+sham group (n = 10), MCAO group (n = 10), EP+MCAO group (n = 10), and EP+MCAO+JAK2/STAT3 pathway agonist (coumermycin A1, CA1) group (n = 10). The results indicated that EP alleviated neurological deficits, reduced infarct volume, and ameliorated neuronal apoptosis induced by MCAO. Additionally, the MCAO‐induced Th17/Treg imbalance could be rectified by EP. The decreased levels of IL‐10 and Foxp3 and increased IL‐17 and RORα in the MCAO group were reversed by EP treatment. Regarding inflammation, EP reduced the concentrations of IL‐6 and IL‐17 and elevated those of IL‐10 and TGF‑β. The neuroprotective effects of EP were accompanied by decreased phosphorylation of JAK2 and STAT3. Furthermore, CA1 pretreatment diminished all the beneficial effects of EP partially. Conclusion Our findings suggest that EP contributes to attenuating neuronal apoptosis, Th17/Treg imbalance, and inflammation induced by MCAO via inhibiting the JAK2/STAT3 pathway, indicating its therapeutic potential in ischemic stroke. |
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| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-13T05:05:19Z |
| publishDate | 2023-06-01 |
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| series | Brain and Behavior |
| spelling | doaj.art-e7b1a1ccd28d48298713568cf416b17b2023-06-16T18:11:55ZengWileyBrain and Behavior2162-32792023-06-01136n/an/a10.1002/brb3.3030Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathwayYuan Shan0Le Wang1Jingying Sun2Sha Chang3Wei Di4Hua Lv5Department of Neurology Shaanxi Provincial People's Hospital Xi'an ChinaDepartment of Neurology Shaanxi Provincial People's Hospital Xi'an ChinaCentral Research Laboratory Shaanxi Provincial People's Hospital Xi'an ChinaDepartment of Neurology Shaanxi Provincial People's Hospital Xi'an ChinaDepartment of Neurology Shaanxi Provincial People's Hospital Xi'an ChinaDepartment of Neurology Shaanxi Provincial People's Hospital Xi'an ChinaAbstract Background Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia‐reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti‐inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)‐induced model. Results Fifty rats were randomly allocated into five groups, including the sham group (n = 10), EP+sham group (n = 10), MCAO group (n = 10), EP+MCAO group (n = 10), and EP+MCAO+JAK2/STAT3 pathway agonist (coumermycin A1, CA1) group (n = 10). The results indicated that EP alleviated neurological deficits, reduced infarct volume, and ameliorated neuronal apoptosis induced by MCAO. Additionally, the MCAO‐induced Th17/Treg imbalance could be rectified by EP. The decreased levels of IL‐10 and Foxp3 and increased IL‐17 and RORα in the MCAO group were reversed by EP treatment. Regarding inflammation, EP reduced the concentrations of IL‐6 and IL‐17 and elevated those of IL‐10 and TGF‑β. The neuroprotective effects of EP were accompanied by decreased phosphorylation of JAK2 and STAT3. Furthermore, CA1 pretreatment diminished all the beneficial effects of EP partially. Conclusion Our findings suggest that EP contributes to attenuating neuronal apoptosis, Th17/Treg imbalance, and inflammation induced by MCAO via inhibiting the JAK2/STAT3 pathway, indicating its therapeutic potential in ischemic stroke.https://doi.org/10.1002/brb3.3030cerebral ischemiaexercise preconditioningJAK2/STAT3 pathwayTh17/Treg balance |
| spellingShingle | Yuan Shan Le Wang Jingying Sun Sha Chang Wei Di Hua Lv Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway Brain and Behavior cerebral ischemia exercise preconditioning JAK2/STAT3 pathway Th17/Treg balance |
| title | Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway |
| title_full | Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway |
| title_fullStr | Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway |
| title_full_unstemmed | Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway |
| title_short | Exercise preconditioning attenuates cerebral ischemia‐induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway |
| title_sort | exercise preconditioning attenuates cerebral ischemia induced neuronal apoptosis th17 treg imbalance and inflammation in rats by inhibiting the jak2 stat3 pathway |
| topic | cerebral ischemia exercise preconditioning JAK2/STAT3 pathway Th17/Treg balance |
| url | https://doi.org/10.1002/brb3.3030 |
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