Early Rehabilitation Exercise after Stroke Improves Neurological Recovery through Enhancing Angiogenesis in Patients and Cerebral Ischemia Rat Model

Abstract

Among cerebrovascular diseases, ischemic stroke is a leading cause of mortality and disability. Thrombolytic therapy with tissue plasminogen activator is the first choice for clinical treatment, but its use is limited due to the high requirements of patient characteristics. Therefore, the choice of neurological rehabilitation strategies after stroke is an important prevention and treatment strategy to promote the recovery of neurological function in patients. This study shows that rehabilitation exercise 24 h after stroke can significantly improve the neurological function (6.47 ± 1.589 vs. 3.21 ± 1.069 and 0.76 ± 0.852), exercise ability (15.68 ± 5.95 vs. 162.32 ± 9.286 and 91.18 ± 7.377), daily living ability (23.37 ± 5.196 vs. 66.95 ± 4.707 and 6.55 ± 2.873), and quality of life (114.39 ± 7.772 vs. 168.61 ± 6.323 and 215.95 ± 10.977) of patients after 1 month and 3 months, and its ability to promote rehabilitation is better than that of rehabilitation exercise administered to patients 72 h after stroke (p < 0.001). Animal experiments show that treadmill exercise 24 h after middle cerebral artery occlusion and reperfusion can inhibit neuronal apoptosis, reduce the volume of cerebral infarction on the third (15.04 ± 1.07% vs. 30.67 ± 3.06%) and fifth (8.33 ± 1.53% vs. 30.67 ± 3.06%) days, and promote the recovery of neurological function on the third (7.22 ± 1.478 vs. 8.28 ± 1.018) and fifth (4.44 ± 0.784 vs. 6.00 ± 0.767) days. Mechanistic studies have shown that treadmill exercise increases the density of microvessels, regulates angiogenesis, and promotes the recovery of nerve function by upregulating the expression of vascular endothelial growth factor and laminin. This study shows that rehabilitation exercise 24 h after stroke is conducive to promoting the recovery of patients’ neurological function, and provides a scientific reference for the clinical rehabilitation of stroke patients.

Keywords: angiogenesis; early rehabilitation; neurological function; stroke.

Figure 1

The cerebral infarction volume were detected with TTC staining method following middle cerebral artery occlusion and treadmill exercise (A) TTC staining method was used to detect brain sections of mouse with middle cerebral artery occlusion and treadmill exercise 1D, 3D and 5D; White is the cerebral infarction area, and red is normal area. (B) Statistical analysis of cerebral infarct volume in (A). (*** p < 0.001 vs. Sham; && p < 0.01, &&& p < 0.001 vs. MCAO) n = 5.

Figure 2

The expression of apoptosis-regulating proteins were detected by Western blot method following middle cerebral artery occlusion and treadmill exercise. (A) The expression level of activated forms of caspase 3 were detected with Western blot in mouse brain with middle cerebral artery occlusion and treadmill exercise 1D, 3D, and 5D; (B) Statistical analysis of the expression level of activated forms of caspase 3 in (A); (C): The expression level of activated forms of caspase 8 were detected with Western blot in mouse brain with middle cerebral artery occlusion and treadmill exercise 1D, 3D, and 5D; (D): Statistical analysis of the expression level of activated forms of caspase 8 in (C). (*** p < 0.001 vs. Sham; &&& p < 0.001 vs. MCAO, n = 3).

Figure 3

The expression of vascular endothelial growth factor were detected by immunofluorescence method follow middle cerebral artery occlusion and treadmill exercise. (A) The expression levels of vascular endothelial growth factor were detected with immunofluorescence in mouse brain with middle cerebral artery occlusion and treadmill exercise 1D, 3D, and 5D; bars: 50 μm; (B) Quantitative analysis of the expression level of a vascular endothelial growth factor in (A). (* p < 0.01 vs. Sham; ## p < 0.01, ### p < 0.001 vs. MCAO, n = 3).

Figure 4

The effect of 24 h treadmill exercise after MCAO on the expression of laminin and mi crovessel density. (A) The laminin expression was detected by immunofluorescence method in the brain of the rats in the Sham, MCAO, 1 day, 3 days, and 5 days in treadmill exercise 24 h after MCAO groups; bars: 50 μm; (B) Quantification of microvessel density as shown by laminin expression (% area stained) in the brain of the rats in the Sham, MCAO, 1 day, 3 days, and 5 days in treadmill exercise 24 h after MCAO group; (C) The laminin expression was detected by Western blot method in the brain of the rats in the Sham, MCAO, 1 day, 3 days and 5 days in treadmill exercise 24 h after MCAO groups. (*** p < 0.001 vs. Sham; # p < 0.01, ### p < 0.001 vs. MCAO, n = 3).

Figure 5

Study flow chart. The time course of this study, inclusion, exclusion, termination criteria, and study groupings are displayed graphically.