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 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.

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats

“…Additionally, EP has also been reported to alleviate memory impairment following CI by protecting hippocampal neurons from ischemia-caused degeneration (Shamsaei et al, 2015). Furthermore, Shan et al (2023) RNA sequencing is proving to be an effective tool in investigating the molecular mechanisms of drugs on diseases . In the present study, we explored RNA sequencing to uncover the potential mechanisms by which EP can mitigate MCAO.…”

Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways

“…Another key factor in liver cell damage is the excessive release of proinflammatory cytokines, and the JAK2/STAT3 pathway plays an important role in this process. 30 Shan et al 59 have shown that exercise preconditioning could reduce neuronal apoptosis and inflammation by inhibiting the JAK2/STAT3 signalling pathway, thus attenuating cerebral ischaemia‒reperfusion injury. Consistent with their findings, our experimental results show that aerobic exercise reduced the phosphorylation of JAK2 and STAT3.…”

Effects of remote ischemic preconditioning in severe traumatic brain injury: A single-center randomized controlled trial

“…[ 27 , 28 ] Second, local chemicals or enzyme-linked reactions are generated during ischemia and reperfusion of distal organs, which subsequently traverse the circulatory pathway to activate receptors and facilitate signal transduction, ultimately mediating neuroprotective effects. [ 29 ] Animal studies conducted previously have also suggested that RIPC can control inflammation, [ 30 ] reduce oxidative stress, [ 31 ] induce apoptosis, [ 32 ] and provide neuroprotection. [ 32 – 34 ] Organ protection is believed to depend on the intricate interaction among these pathways.…”