Exercise rehabilitation immediately following ischemic stroke exacerbates inflammatory injury

Li, Fengwu; Pendy, John T.; Ding, Jessie N; Peng, Changya; Li, Xiaorong; Shen, Jingjing; Wang, Sainan; Xu, Geng

doi:10.1080/01616412.2017.1315882

Cited by 55 publications

(41 citation statements)

References 38 publications

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“…The early improvement in infarct volume seen in these results aligned with a previous meta-analysis, in which infarct volume was reduced most effectively by exercise administered with the shortest delays after ischemia (Egan et al, 2014 ); data from our group derived from pre-conditioning experimentation suggest that this may be related to the capacity of exercise to mitigate inflammatory damage during reperfusion (Ding et al, 2005 ), with the caveat that the exercise initiation too early after ischemia may be detrimental (Li et al, 2017a ). More recent work by our group further substantiated these findings by demonstrating that exercise improved glycometabolism in the ischemic area and decreased neuroinflammation and apoptosis as early as 1 day post-stroke, and also at 3 days (Shen et al, 2016 ; Li et al, 2017a , b , c ). These findings suggest that it is beneficial to initiate exercise early after ischemia/reperfusion, as was done in the present study.…”

Section: Discussionmentioning

confidence: 64%

“…At 3 days of ischemia and reperfusion in rats that underwent MCAO, brains were resected and cut into 2-mm-thick slices, which were then treated with 2,3,5-triphenyltetrazolium chloride (TTC; Sigma–Aldrich, St. Louis, MO, USA) for staining (Li et al, 2017b ), facilitating the use of an indirect method for calculating infarct volume to minimize error caused by edema.…”

Section: Methodsmentioning

confidence: 99%

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In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Huber

et al. 2020

Front. Cell. Neurosci.

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Although physical exercise has been demonstrated to augment recovery of the post-stroke brain, the question of what level of exercise intensity optimizes neurological outcomes of post-stroke rehabilitation remains unsettled. In this study, we aim to clarify the mechanisms underlying the intensity-dependent effect of exercise on neurologic function, and thereby to help direct the clinical application of exercisebased neurorehabilitation. To do this, we used a well-established rat model of ischemic stroke consisting of cerebral ischemia induction through middle cerebral artery occlusion (MCAO). Ischemic rats were subsequently assigned either to a control group entailing post-stroke rest or to one of two exercise groups distinguished by the intensity of their accompanying treadmill regimens. After 24 h of reperfusion, exercise was initiated. Infarct volume, apoptotic cell death, and neurological defects were quantified in all groups at 3 days, and motor and cognitive functions were tracked up to day-28. Additionally, Western blotting was used to assess the influence of our interventions on several proteins related to synaptogenesis and neuroplasticity (growth-associated protein 43, a microtubule-associated protein, postsynaptic density-95, synapsin I, hypoxia-inducible factor-1α, brain-derived neurotrophic factor, nerve growth factor, tyrosine kinase B, and cAMP response element-binding protein). Our results were in equal parts encouraging and surprising. Both mild and intense exercise significantly decreased infarct volume, cell death, and neurological deficits. Motor and cognitive function, as determined using an array of tests such as beam balance, forelimb placing, and the Morris water maze, were also significantly improved by both exercise protocols. Interestingly, while an obvious enhancement of neuroplasticity proteins was shown in both exercise groups, mild exercise rats demonstrated a stronger effect on the expressions of Tau (p < 0.01), brain-derived neurotrophic factor (p < 0.01), and tyrosine kinase B (p < 0.05). These findings contribute to the growing body of literature regarding the positive effects of both mild and intense long-term treadmill exercise on brain injury, functional outcome, and

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Section: Discussionmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Huber

et al. 2020

Front. Cell. Neurosci.

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“…All animals were sacrificed at the same time points: 24 h after forced exercise for detection of infarct volume, 30 min after exercise for quick detection of levels of ATP, NADH and ROS, 24 h for cell death detection, as well as at 3 h and 24 h after exercise termination for later protein expression of angiogenic growth factors. All of the time points for animal sacrifice from this study were based on previous studies (Kochanski et al, 2013; Geng et al, 2016; Shen et al, 2016; Li et al, 2017). The mortality rate was low (less than 10%) and was about equal between paired groups (i.e., stroke groups with or without exercise).…”

Section: Methodsmentioning

confidence: 99%

Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise Initiation Timing

Khan

et al. 2017

Front. Cell. Neurosci.

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Accumulating evidence has demonstrated that post-stroke physical rehabilitation may reduce morbidity. The effectiveness of post-stroke exercise, however, appears to be contingent upon exercise initiation. This study assessed the hypothesis that very early exercise exacerbates brain injury, induces reactive oxygen species (ROS) generation, and promotes energy failure. A total of 230 adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion for 2 h, and randomized into eight groups, including two sham injury control groups, three non-exercise and three exercise groups. Exercise was initiated after 6 h, 24 h and 3 days of reperfusion. Twenty-four hours after completion of exercise (and at corresponding time points in non-exercise controls), infarct volumes and apoptotic cell death were examined. Early brain oxidative metabolism was quantified by examining ROS, ATP and NADH levels 0.5 h after completion of exercise. Furthermore, protein expressions of angiogenic growth factors were measured in order to determine whether post-stroke angiogenesis played a role in rehabilitation. As expected, ischemic stroke resulted in brain infarction, apoptotic cell death and ROS generation, and diminished NADH and ATP production. Infarct volumes and apoptotic cell death were enhanced (p < 0.05) by exercise that was initiated after 6 h of reperfusion, but decreased by late exercise (24 h, 3 days). This exacerbated brain injury at 6 h was associated with increased ROS levels (p < 0.05), and decreased (p < 0.05) NADH and ATP levels. In conclusion, very early exercise aggravated brain damage, and early exercise-induced energy failure with ROS generation may underlie the exacerbation of brain injury. These results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.

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“…Li et al found that exercise beginning 6–24 h post-stroke led to an increase in inflammatory cytokines, whereas the same exercise commencing 3 days post-stroke decreased those cytokines [43]. Likewise, Risedal et al found that exercise training in rats beginning at 24 h post-stroke was associated with enlargement of ischemic lesions compared with animals who began training at 7 days, though the early and late training groups performed similarly on behavioral tests [44].…”

Section: Neuroplastic Changes Following Strokementioning

confidence: 99%

Early Rehabilitation After Stroke: a Narrative Review

Coleman

Moudgal

Lang

et al. 2017

Curr Atheroscler Rep

286

195

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Purpose of Review Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain’s dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Recent Findings Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. Summary The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

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Exercise rehabilitation immediately following ischemic stroke exacerbates inflammatory injury

Cited by 55 publications

References 38 publications

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise Initiation Timing

Early Rehabilitation After Stroke: a Narrative Review

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