Exercise Therapy Augments the Ischemia-Induced Proangiogenic State and Results in Sustained Improvement after Stroke (original) (raw)
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Neurological Research, 2010
Although the favorable effects of physical exercise in neurorehabilitation after traumatic brain injury (TBI) are well known, detailed pathologic and functional alterations exerted by previous physical exercise on posttraumatic cerebral inflammation have been limited. In the present study, it is showed that fluid percussion brain injury (FPI) induced motor function impairment, followed by increased plasma fluorescein extravasation and cerebral-inflammation characterized by interleukin-1b, tumor necrosis factor-a (TNF-a) increase, and decreased IL-10. In addition, myeloperoxidase (MPO) increase and Na ? ,K ? -ATPase activity inhibition after FPI suggest that the opening of blood-brain barrier (BBB) followed by neurtrophils infiltration and cerebral inflammation may contribute to the failure of selected targets leading to secondary damage. In fact, Pearson's correlation analysis revealed strong correlation of MPO activity increase with Na ? ,K ? -ATPase activity inhibition in sedentary rats. Statistical analysis also revealed that previous running exercise (4 weeks) protected against FPI-induced motor function impairment and fluorescein extravasation. Previous physical training also induced IL-10 increase per se and protected against cerebral IL-1b, and TNF-a increase and IL-10 decrease induced by FPI. This protocol of physical training was effective against MPO activity increase and Na ? ,K ? -ATPase activity inhibition after FPI. The present protection correlated with MPO activity decrease suggests that the alteration of cerebral inflammatory status profile elicited by previous physical training reduces initial damage and limits long-term secondary degeneration after TBI. This prophylactic effect may facilitate functional recovery in patients suffering from brain injury induced by TBI.
Neuroscience, 2005
The optimal amount of endurance exercise required to elevate proteins involved in neuroplasticity during stroke rehabilitation is not known. This study compared the effects of varying intensities and durations of endurance exercise using both motorized and voluntary running wheels after endothelin-I-induced focal ischemia in rats. Hippocampal levels of brain-derived neurotrophic factor, insulin-like growth factor I and synapsin-I were elevated in the ischemic hemisphere even in sedentary animals suggesting an intrinsic restorative response 2 weeks after ischemia. In the sensorimotor cortex and the hippocampus of the intact hemisphere, one episode of moderate walking exercise, but not more intense running, resulted in the greatest increases in levels of brain-derived neurotrophic factor and synapsin-I. Exercise did not increase brain-derived neurotrophic factor, insulin-like growth factor I or synapsin-I in the ischemic hemisphere. In voluntary running animals, both brain and serum insulin-like growth factor I appeared to be intensity dependent and were associated with decreasing serum levels of insulin-like growth factor I and increasing hippocampal levels of insulin-like growth factor I in the ischemic hemisphere. This supports the notion that exercise facilitates the movement of insulin-like growth factor I across the blood-brain barrier. Serum corticosterone levels were elevated by all exercise regimens and were highest in rats exposed to motorized running of greater speed or duration. The elevation of corticosterone did not seem to alter the expression of the proteins measured, however, graduated exercise protocols may be indicated early after stroke. These findings suggest that relatively modest exercise intervention can increase proteins involved in synaptic plasticity in areas of the brain that likely subserve motor relearning after stroke.
Introduction: Cerebral ischemia and reperfusion causes physiological and biochemical changes in the neuronal cells that will eventually lead to cell damage. Evidence indicates that exercise reduces the ischemia and reperfusion-induced brain damages in animal models of stroke. In the present study, the effect of exercise preconditioning on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats was investigated. Methods: Twenty-one adult male wistar rats (weighing 260-300 g) were randomly divided into three groups: sham operated, exercise plus ischemia, and ischemia group (7 rats per group). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Transient focal cerebral ischemia and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by reperfusion for 23 hours. After 24 hours ischemia, movement disorders were tested by a special neurological examination. Also, cerebral edema was assessed by determining the brain water content. Results: The results showed that pre-ischemic exercise significantly reduced brain edema (P<0.05). In addition, exercise preconditioning decreased the neurological movement disorders caused by brain ischemia and reperfusion (P<0.05). Conclusion: Preconditioning by exercise had neuroprotective effects against brain ischemia and reperfusion-induced edema and movement disorders. Thus, it could be considered as a useful strategy for prevention of ischemic injuries, especially in people at risk.
Gene, Cell and Tissue, 2020
Background: Physical activity and dynamic lifestyle play an important role in the prevention and treatment of some common neurological diseases. One valuable approach to increasing health and reducing brain damage is to perform an exercise and physical activity. Objectives: The aim of the present study was to investigate the effect of exercise pre-training on the intervening factors and complications of cerebral ischemia. Methods: In this study, forty Wistar rats were randomly divided into four groups, including (1) endurance training, (2) endurancecognitive training, (3) ischemia, and (4) control. The training was performed for 3 weeks. After the last training session, the rats had to undergo cerebral ischemia. The ischemia was induced by occlusion of both common carotid arteries for 30 min. Real-time PCR method was used to measure the expression level of TrkB, Bax, and Bcl-2 genes. Results: The levels of TrkB gene expression were significantly increased in the endurance training and endurance-cognitive training groups compared to the ischemia and control groups (P < 0.05). There was a significant increase in the levels of Bcl-2 gene expression in the endurance training group compared to the ischemia group as well as the endurance-cognitive group compared to the ischemia and control groups (P < 0.05). Also, the levels of Bax gene expression in the endurance training and endurance-cognitive groups were significantly lower than the control group (P < 0.05). Conclusions: This study showed that exercise as a preconditioning stimulus has neuroprotective effects against cerebral ischemia.
Effect of Exercise Type on Vascular Stabilization Factor in Ischemic Stroke Patients
Journal of Evolution of Medical and Dental Sciences
BACKGROUND Stroke is one of the leading causes of mortality and disability in the world. The angiogenesis strategy is a new therapeutic approach to exercise in these patients. The purpose of this study was to investigate the effect of continuous exercise on serum levels of vascular stabilizing factor and its consequences. METHODS In this randomized clinical trial study, 30 patients with stroke who volunteered to participate in the study, aged 45-65 years, were selected by convenience sampling and non-random sampling method. Subjects were randomly selected. The patients were randomly divided into intervention group (4 weeks of continuous exercise in 40-60 minutes pedal with 60-65% VO2 peak intensity for 5 days per week and physiotherapy) and control group (physiotherapy only). Blood angiogenesis and motor function levels were measured at baseline and twenty-eight days after the last exercise session. Data was analyzed by using Stata software version 13 at the significance level of 0.05. RESULTS In this trial, thirty patients completed the study period, and were included in the analysis. The mean ages of patients in the control and intervention groups were 55.66 (S.D.: 6.69) and 61.46 (S.D.: 6.47) years, respectively. Serum levels of angiopoietin-1 increased after exercise at alpha level (P = 0.011). The reduction of the Modified Rankin Scale was obtained as a secondary consequence (P = 0.001). CONCLUSIONS Continuous exercise training over four weeks can improve the prognosis of patients by altering the levels of angiogenesis-stabilizing factor in decreasing the symptoms of stroke.
Acta Neuropathologica, 2012
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, which also has neuroprotective activity. In view of these dual actions on vessels and neurons, we were interested whether VEGF promotes long distance axonal plasticity in the ischemic brain. Herein, we show that VEGF promotes neurological stroke recovery in mice when delivered in a delayed way starting 3 days after middle cerebral artery occlusion. Using anterograde tracttracing experiments that we combined with histochemical and molecular biological studies, we demonstrate that although VEGF promoted angiogenesis predominantly in the ischemic hemisphere, pronounced axonal sprouting was induced by VEGF in the contralesional, but not the ipsilesional corticobulbar system. Corticobulbar plasticity was accompanied by the deactivation of the matrix metalloproteinase MMP9 in the lesioned hemisphere and the transient downregulation of the axonal growth inhibitors NG2 proteoglycan and brevican and the guidance molecules ephrin B1/2 in the contralesional hemisphere. The regulation of matrix proteinases, growth inhibitors, and guidance molecules offers insights how brain plasticity is controlled in the ischemic brain.
Frontiers in neurology, 2018
Rehabilitation therapy is the only available treatment for stroke survivors presenting neurological deficits; however, the underlying molecules and mechanisms associated with functional/motor improvement during rehabilitation are poorly understood. Our aim is to study the modulation of angiogenin and endothelial progenitor cells (EPCs) as repair-associated factors in a cohort of stroke patients and mouse models of rehabilitation after cerebral ischemia. The clinical study included 18 ischemic strokes admitted to an intensive rehabilitation therapy (IRT) unit, 18 non-ischemic controls and brain samples from three deceased patients. Angiogenin and EPCs were measured in blood obtained before and up to 6 months after IRT together with an extensive evaluation of the motor/functional status. In parallel, C57BL/6 mice underwent middle cerebral artery occlusion, and the pasta matrix reaching-task or treadmill exercises were used as rehabilitation models. Angiogenin RNA expression was measur...
Brain Research, 2006
Vascular endothelial growth factor (VEGF) is an angiogenesis factor with neurotrophic, neuroprotective and neuroproliferative effects. Depending on the dose, route and time of administration in relation to focal cerebral ischemia, VEGF can improve histological outcome and sensorimotor function in rodents. However, VEGF also increases vascular permeability, which can lead to brain edema and exacerbate ischemic brain injury. Thus, although VEGF is a candidate therapeutic for stroke and other ischemic disorders, its benefit relative to risk is uncertain. Considering that functional rather than histological measures of outcome are probably most relevant to therapeutic prospects for human stroke, we investigated the effects of VEGF after middle cerebral artery occlusion in rats using a series of behavioral tests. We report that VEGF improves functional outcome in ischemic rats, including both sensorimotor and cognitive deficiencies.
Effects of vascular endothelial growth factor in ischemic stroke
Journal of Neuroscience Research, 2012
Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that is crucially involved in neurovascular remodeling in the ischemic brain. VEGF promotes angiogenesis, protects ischemic neurons from injury, has potent anti-inflammatory actions, and promotes brain plasticity, in addition to enhancing the recruitment and proliferation of neural precursor cells. These broad actions make VEGF interesting as a model molecule that allows understanding endogenous responses of the brain to injuries. However, several studies indicate that the route and timing of VEGF administration are crucial for the effects of VEGF on ischemic brain tissue. Hence, systemic VEGF delivery in the very acute stroke phase may exacerbate brain damage because of the promotion of blood-brain barrier breakdown that inevitably accompanies vascular growth. Future studies aimed at the promotion of neurovascular remodeling in ischemic stroke should carefully take into consideration pleiotropic actions of angiogenic growth factors beyond vascular growth. V
2018
Ischemic stroke remains one of the leading causes of long-term disability and death worldwide, despite being a preventable neurological injury. Efforts in prevention have included urging patients toward a healthier lifestyle, including a healthy diet and regular exercise. Experimental and clinical evidence supporting these healthy-living recommendations found that systemic interventions like exercise impart protection for both rodents and humans. Despite these data, patients who are at the highest risk for stroke are unlikely to make these long-term lifestyle changes. Herein lies a challenge for clinicians and researchers alike to identify pharmaceutical or physical substitutions for exercise (e.g. limb remote ischemic conditioning (RIC)) that can be administered upon identification of a stroke, or a high risk of stroke, in the clinic. One impact of exercise is to promote vascular remodeling in the skeletal muscle. A chief component of this remodeling is proteolysis of the vascular ...