Physical exercise is becoming a prominent therapeutic strategy to improve stroke outcomes. It was previously shown that long term exercise reduces infarct volume, but this was never tested in acute short term preconditioning exercise in a thromboembolic model of stroke. Exercise induced shear stress improves vascular function through increased activity of endothelial nitric oxide synthase (eNOS) and its upstream principal activator, AMP-activated protein kinase (AMPK). However, this was not previously tested in a stroke setting. Accordingly, we tested the hypothesis that acute short term preconditioning exercise improves stroke outcomes through increased AMPK and eNOS activity.
Methods: Male Wistar rats (300g) were subjected to treadmill exercise for four days (25 minutes/day), break for 2 days and then one acute bout for 30 minutes. Exercised animals were subjected to thromboembolic stroke at 1h, 6h or 24h after the last exercise session. At 24h, control (sedentary) and exercised rats were tested for neurological outcomes, infarct size and edema. Western Blotting was used to measure the expression of active eNOS (p-S1177-eNOS) and active AMPK (p-T172-AMPK).
Results: Acute exercise significantly reduced infarct size and edema and improved functional outcomes compared to control. It also significantly increased the expression of peNOS and pAMPK in the brain, cerebral vessels and aorta (Table).
Conclusion: Acute exercise preconditioning significantly reduced neurovascular injury and improved functional outcome after stroke through increased eNOS activity. Our findings are novel to point out the role of preconditioning exercise induced AMPK and eNOS activation in improving stroke outcomes.