Objectives: The rehabilitative benefits of physical exercise after stroke appear to be contingent upon exercise initiation timing. The present study assessed the hypothesis that very early post-stroke exercise would amplify cellular stress and increases expression of pro-inflammatory mediators, while exercise initiated later would limit the inflammation associated with cerebral ischemia/reperfusion injury.
Methods: Adult rats were subjected to middle cerebral artery occlusion and subsequently assigned to one of seven groups: one sham injury control group, three stroke groups subjected to exercise initiated after 6, 24 hours, or 3 days of reperfusion, and three stroke groups not subjected to exercise. Expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were examined 3 and 24 hours after completion of exercise regimens (and at corresponding time points in non-exercise controls). Heat shock protein-70 (Hsp70) and hypoxia inducible factor-1α (HIF-1α) expression levels were also compared between exercise and non-exercise groups.
Results: Early post-stroke exercise was associated with increased expression of pro-inflammatory mediators (ICAM-1, VCAM-1, TNF-α, and IL-1β) and increased expression of cell stress markers (Hsp70 and HIF-1α). Exercise initiated after 3 days of reperfusion was associated with decreased expression of these molecules.
Conclusion: Post-stroke exercise, if too early, may result in elevated levels of cell stress and increased expression of pro-inflammatory cytokines, which may amplify the tissue damage associated with cerebral ischemia/reperfusion injury. The results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.
Keywords: HIF-1α; Hsp70; ICAM-1; IL-1β; Ischemia/reperfusion injury; VCAM-1 TNF-α; rehabilitation.