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

Figures

• 

  Figure 1. (A) 2,3,5-Triphenyltetrazolium chloride (TTC) staining illustrating infarct volumes in ischemic rats (subjected to 2-h middle cerebral artery (MCA) occlusion) with or without exercise initiated at 6 h, 24 h and 3 days after reperfusion. (B) In contrast to the non-exercise groups, very early exercise at 6 h largely (*p < 0.05) increased neural damage, while the later exercise groups conducted at 24 h and 3 days after reperfusion demonstrated a significant (#p < 0.05) reduction in apoptosis.

• 

  Figure 2. (A) Comparison of mild and intense exercise (initiated at 6 h, 24 h and 3 days of reperfusion) on infarct volume determined by TTC. (B) Compared to the intense exercise groups, infarct volumes of the mild exercise groups were slightly but not significantly increased after all exercise time points.

• 

  Figure 3. (A) Apoptotic cell death detected using ELISA was measured 24 h after exercise termination or the equivalent time point in non-exercise animals. One-way ANOVA of non-exercise groups indicated a significant (**p < 0.01) increase in all non-exercise ischemic rat groups (6 h, 24 h and 3 day) compared to sham-operation controls. (B) In contrast to non-exercise groups, The student t-test indicates that very early exercise initiated at 6 h of reperfusion significantly (*p < 0.05) increased cell death, while groups in which exercise was initiated after 24 h and 3 days of reperfusion exhibited non-significant reductions in apoptosis.

• 

  Figure 4. (A) TUNEL of non-exercise and exercise groups (initiated at 6 h, 24 h and 3 days of reperfusion). (B) Compared to stroke groups without exercise, apoptotic cell death was significantly (*p < 0.05) increased after very early exercise (initiated at 6 h of reperfusion), while later exercise (24 h and 3 days) significantly (#p < 0.05) reduced cell death as compared to non-exercise stroke group.

• 

  Figure 5. (A) Reactive oxygen species (ROS) levels were examined 0.5 h after exercise termination in ischemic rats with exercise and at equivalent time points in ischemic rats without exercise. Compared to sham controls (reference as 1, not shown), ischemic animals exhibited significantly increased ROS levels. Further increases in ROS production were observed in the early (6 h and 24 h, *p < 0.05) exercise groups as compared to non-exercise controls. Late exercise (initiated after 3 days of reperfusion) did not have a significant impact on ROS levels, as compared to non-exercise ischemic rats. (B) ATP levels were examined 0.5 h after exercise termination in exercise groups and at equivalent time points in non-exercise controls. MCA occlusion significantly decreased ATP production as compared to sham controls (reference as 1, not shown). Early exercise groups (6 h and 24 h, #p < 0.05), though not the late exercise group (3 days), exhibited further reductions in ATP levels as compared to non-exercise controls. (C) NADH levels, measured 0.5 h after exercise termination in exercise groups and at equivalent time points in ischemic rats, were significantly decreased in all non-exercise ischemic…

• 

  Figure 6. Based on sham control (reference as 1, not shown), angiopoietin-1 (Ang-1) expression at 3 h after exercise termination was slightly increased in exercise groups compared to non-exercise ischemic rat groups at 6 h, 24 h and 3 days after reperfusion (A). A significantly enhanced increase in Ang-1 protein expression at 24 h after exercise termination was observed in the very early (6 h; *p < 0.05) and late (3 days; **p < 0.01) exercise groups while a slight increase was seen in the 24 h exercise group (B). Angiopoietin-2 (Ang-2) protein expression was measured 3 and 24 h after exercise termination or the equivalent period (C,D). At 3 h, late exercise (3 days) resulted in a significant (*p < 0.05) increase in Ang-2 protein expression compared to non-exercise ischemic rat groups, while no changes were seen with early exercise (6 and 24 h). For 24 h after exercise termination, exercise at three time points resulted in an increase in Ang-2 protein expression, although they did not reach a significant level. (E) Vascular endothelial growth factor (VEGF) protein expression was measured 3 h after exercise termination or the equivalent period. Only late exercise (3 days) significantly (**p…