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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. © 2013 Wiley Periodicals, Inc.
Journal of Neuroscience Research 03/2013; · 2.74 Impact Factor
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ABSTRACT: The neuroprotective nature of exercise has been well established and the mechanisms of this protection are still a subject of much research. This study aims to determine if cerebral blood flow is constituently higher during the ischemia or reperfusion events in stroke.
Adult male Sprague-Dawley rats were randomly assigned into exercise or non-exercise (control) groups. Exercised rats underwent 30 minutes of running on a treadmill for 3 weeks. A 2 hour unilateral middle cerebral artery occlusion using an intraluminal filament was performed to induce ischemic stroke, followed by a 24 hour reperfusion. A sham control without exercise and middle cerebral artery occlusion was used. Laser Doppler flowmetry (LDF) and (15)O-H(2)O positron emission tomography (PET) were used to determine cerebral blood flow, respectively. (18)F-fluorodeoxy-D-glucose was used to determine cerebral metabolism in some animals. Histological analysis determined infarct volume in the same animal after blood flow examination.
LDF and PET both indicated that middle cerebral artery occlusion significantly (p<0.05) reduced cerebral blood flow during ischemia and reperfusion in association with reduced cerebral metabolism after stroke. However, pre-ischemic exercise significantly (p<0.05) improved cerebral blood flow during reperfusion, although cerebral blood flow remained at a similar level to that of the non-exercise stroke group during the middle cerebral artery occlusion. This improved cerebral blood flow during reperfusion was associated with decreased brain infarct volume.
This study revealed that pre-ischemic exercise in rats improved cerebral blood flow during reperfusion, suggesting that exercise provides neuroprotection by partially ameliorating the 'no reflow' phenomenon in stroke.
Neurological Research 06/2010; 32(5):523-9. · 1.52 Impact Factor
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ABSTRACT: We sought to determine whether cerebral inflammation in ischemic rats was reduced by a neuroprotective action of pre-ischemic tumor necrosis factor-alpha up-regulation, which down-regulated matrix metalloproteinase-9 activity via extracellular signal-regulated kinase 1/2 phosphorylation.
Adult male Sprague-Dawley rats were subjected to 30 minutes of exercise on a treadmill for 3 weeks. Stroke was induced by a 2 hour middle cerebral artery occlusion using an intraluminal filament. The exercised animals were treated with tumor necrosis factor-alpha antibody, UO126 (extracellular signal-regulated kinase 1/2 inhibitor), or both UO126 and doxycycline (matrix metalloproteinase-9 inhibitor). Brain infarct volume was assessed using Nissl staining. Leukocyte infiltration was evaluated using myeloperoxidase immunostaining. Intercellular adhesion molecule-1 and matrix metalloproteinase protein levels were determined by Western blot, and enzyme activity was evaluated using zymography.
There was a significant decrease in neurological deficits, brain infarct volume and leukocyte infiltration, in association with reduction in matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression in exercised animals. Exercised animals treated with either tumor necrosis factor-alpha antibody or with UO126 showed a reversal of neurological outcome, infarct volume and leukocyte infiltration. Matrix metalloproteinase-9 activity was reversed, at least partially, but the intercellular adhesion molecule-1 expression was not. Neuroprotection remained when the exercised ischemic rats were treated with both UO126 and doxycycline.
These results suggest that exercise-induced up-regulation of tumor necrosis factor-alpha before stroke and extracellular signal-regulated kinase 1/2 phosphorylation play a role in decreasing brain inflammation by regulating matrix metalloproteinase-9 activity.
Neurological Research 09/2009; 32(7):756-62. · 1.52 Impact Factor
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ABSTRACT: As part of the innate immune system, activation of Toll-like receptor-4 by inflammatory mediators causes the release of inflammatory cytokines, leading to cellular damage. Exercise for 3 weeks has been shown to provide neuroprotection against ischemia/reperfusion insults by decreasing inflammation. This study explores the expression of Toll-like receptor-4 in brain parenchyma during an ischemic stroke after exercise, in association with brain injury.
Adult male Sprague-Dawley rats were studied in four groups (control, exercise, stroke and stroke after exercise). Exercise consisted of 30 minutes of treadmill running daily for 3 weeks. Using an intraluminal filament, a stroke was induced by 2 hour middle cerebral artery occlusion. Nissl staining was used to determine brain infarct volume. Brain Toll-like receptor-4 messenger RNA expression and protein levels were determined by real time reverse transcriptase polymerase chain reaction and Western blot, respectively.
Exercise significantly (p<0.05) decreased Toll-like receptor-4 messenger RNA and protein expression, in association with significantly (p<0.05) reduced brain infarct volume. The stroke group had significantly (p<0.05) increased levels of Toll-like receptor-4 expression compared to the control, whereas the exercise/stroke group was significantly (p<0.05) attenuated.
Exercise reduced Toll-like receptor-4 expression within brain tissue in response to ischemia/reperfusion insult. This is the first paper, to our knowledge, indicating the correlation between exercise, Toll-like receptor-4 expression and reduced brain infarct volume.
Neurological Research 09/2009; 32(2):123-6. · 1.52 Impact Factor
