Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury

Abstract

Physical exercise preconditioning is known to ameliorate stroke-induced injury. In addition to several other mechanisms, the beneficial effect of preischemic exercise following stroke is due to an upregulated capacity to maintain energy supplies. Adult male Sprague-Dawley rats were used in exercise and control groups. After 1-3 weeks of exercise, several enzymes were analyzed as a gauge of the direct effect of physical exercise on cerebral metabolism. As a measure of metabolic capacity, an ADP/ATP ratio was obtained. Glucose transporters (GLUT1 and GLUT3) were monitored to assess glucose influx, and phosphofructokinase (PFK) was measured to determine the rate of glycolysis. Hypoxia-induced factor-1α (HIF-1α) and 5'AMP-activated protein kinase (AMPK) levels were also determined. These same analyses were performed on preconditioned and control rats following an ischemic/reperfusion (I/R) insult. Our results show that GLUT1, GLUT3, PFK, AMPK, and HIF-1α were all increased following 3 weeks of exercise training. In addition, the ADP/ATP ratio was chronically elevated during these 3 weeks. After I/R injury, HIF-1α and AMPK were significantly higher in exercised rats. The ADP/ATP ratio was reduced in preconditioned rats in the acute phase after stroke, suggesting a lower level of metabolic disorder. GLUT1 and GLUT3 were also increased in the acute phase in exercise rats, indicating that these rats were better able to increase rates of metabolism immediately after ischemic injury. In addition, PFK expression was increased in exercise rats showing an enhanced glycolysis resulting from exercise preconditioning. Altogether, exercise preconditioning increased the rates of glucose metabolism, allowing a more rapid and more substantial increase in ATP production following stroke.

Exercise Preconditioning Regulates the Toll-Like Receptor 4/Nuclear Factor-κB Signaling Pathway and Reduces Cerebral Ischemia/Reperfusion Inflammatory Injury: A Study in Rats

“…Previous studies have demonstrated that EP can improve BBB function, reduce the severity of ischemic brain injury, 30,31 improve cerebral blood flow, regulate the expression of endothelin-1, and improve neurological deficits 32 after cerebral ischemia by regulating imbalances in MMP-9 and TIMP-1 expression. EP is also reported to interact with superoxide dismutase, reduce malondialdehyde accumulation, and enhance cellular antioxidant capacity.…”

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

“…Importantly, clinical studies in stroke patients conducted in the early 1970s first reported that the energy requirements of patients with hemiparetic gait were elevated by 55%–100% compared to normal controls (Corcoran et al, 1970; Gersten and Orr, 1971). In animal studies, hypoxic stress and forced post-stroke physical exercise result in an increased demand for ATP-generating capacity and elevated glucose metabolism in the brain (Kinni et al, 2011; Dornbos et al, 2013). Together, these results indicate that exercise increases the metabolic activity of the brain, driving it to consume more energy via glycolysis.…”

Enhanced apoptosis from early physical exercise rehabilitation following ischemic stroke

“…Postinjury exercise therapy that aims to ameliorate physical disability after stroke has long been considered a logical candidate for neuroprotective rehabilitation (Arya et al, 2011). In previous studies, neuroprotection has been consistently evidenced by physical exercise through reduced sequelae of brain infarction with improved functional outcomes in a rat ischemic stroke model (Ding et al, 2006;Dornbos et al, 2013;Q.W. Zhang et al, 2013).…”