![]() Alternatively, exercise conditioning is believed to be an effective strategy that attenuates the detrimental effects of ischemia and enhances various cognitive abilities, such as motor function ( Thijssen et al., 2018). In this rehabilitative method, cycles of transient ischemia to the distal limbs after a vascular accident, such as a stroke, stimulate physiologic responses that confer protection to the ischemic brain ( Zhao J. ![]() Ischemic postconditioning is one of the strategies widely used to attenuate stroke-induced neural damage in animals and humans ( Landman et al., 2019). et al., 2020) to improve the prognosis and quality of life in stroke victims. Various conditioning strategies play important roles in reducing ischemic and reperfusion injury from stroke ( Serviddio et al., 2008 Lemoine et al., 2017 Wang J. Despite growing approaches to treatment, many patients are left with a lifelong disability. Stroke is the third leading cause of mortality and disability worldwide ( Xiang et al., 2019 Turon et al., 2020). The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well. Additionally, the results may provide a base for our future study regarding the regulation of SIRT1 on the ROS/ER stress pathway in the biochemical processes underlying post-stroke neuroprotection. Additionally, both PostE groups saw significant increases in SIRT1 expression.In this study, both mild and intense PostE levels induced neuroprotection after stroke through SIRT1 and ROS/ER stress pathway. Both PostE groups saw decreases in ER stress proteins, while MPostE demonstrated a further reduction in GRP78 (*** p < 0.001) and Caspase-12 (* p < 0.05) expressions at 1 day and IRE1α (** p < 0.01) and CHOP (* p < 0.05) expressions at 3 days. MPostE further increased Bcl-2 expression and Bcl-2/BAX ratio as well as BAX and Caspase-3 expressions and ROS production (* p < 0.05). ROS production was detected by flow cytometry.Compared to resting rats, both MPostE and IPostE significantly decreased brain infarct volumes and edema, neurological deficits, ROS production, and apoptotic cell death. At 1 and 3 days thereafter, we determined infarct volumes, neurological defects, brain edema, apoptotic cell death through measuring pro- (BAX and Caspase-3) and anti-apoptotic (Bcl-2) proteins, and ER stress through the measurement of glucose-regulated protein 78 (GRP78), inositol-requiring 1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), Caspase-12, and SIRT1. PostE was initiated 24 h after reperfusion and performed on a treadmill. Adult rats were subjected to middle cerebral artery occlusion (MCAO) followed by either: (1) resting (2) mild exercise postconditioning (MPostE) or (3) intense exercise postconditioning (IPostE). The present study investigated whether exercise postconditioning (PostE) induced neuroprotection and elucidated the involvement of SIRT1 regulation on the ROS/ER stress pathway. While it is well-known that pre-stroke exercise conditioning reduces the incidence of stroke and the development of comorbidities, it is unclear whether post-stroke exercise conditioning is also neuroprotective. Dingell VA Medical Center, Detroit, MI, United States 4Department of Research and Development Center, John D.3Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States.2Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.1China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.Fengwu Li 1, Xiaokun Geng 1,2,3*, Hangil Lee 3, Melissa Wills 3 and Yuchuan Ding 3,4*
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