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Short-Term Acute Exercise Preconditioning Reduces Neurovascular Injury After Stroke Through Induced eNOS Activation

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Abstract

Physical exercise is known to reduce cardiovascular risk but its role in ischemic stroke is not clear. It was previously shown that an acute single bout of exercise reduced increased eNOS activation in the heart and reduced myocardial infarction. However, the impact of a single bout or short-term exercise on eNOS-induced neuroprotection after stroke was not previously studied. Accordingly, this study was designed to test the hypothesis that short-term acute exercise can provide “immediate neuroprotection” and improve stroke outcomes through induced eNOS activation. Male Wistar rats (300 g) were subjected to HIIT treadmill exercise for 4 days (25 min/day), break for 2 days, and then one acute bout for 30 min. Exercised animals were subjected to thromboembolic stroke 1 h, 6 h, 24 h, or 72 h after the last exercise session. At 24 h after stroke, control (sedentary) and exercised rats were tested for neurological outcomes, infarct size, and edema. The expression of active eNOS (p-S1177-eNOS) and active AMPK (p-T172-AMPK) was measured in the brain, cerebral vessels, and aorta. In an additional cohort, animals were treated with the eNOS inhibitor, L-NIO (I.P, 20 mg/kg), and stroked 1 h after exercise and compared with non-exercise animals. Acute exercise significantly reduced infarct size, edema, and improved functional outcomes, and significantly increased the expression of peNOS and pAMPK in the brain, cerebral vessels, and aorta. eNOS inhibition abolished the exercise-induced improvement in outcomes. Short-term acute preconditioning exercise reduced the neurovascular injury and improved functional outcomes after stroke through eNOS activation.

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Funding

This work was supported by NIH Award R01 NS099455 A1 to David C. Hess.

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Authors and Affiliations

  1. Department of Neurology, Augusta University, Augusta, GA, 30912, USA

    Sherif Hafez, Mohammad Badruzzaman Khan, Jesse D. Wagner & David C. Hess

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, 18301 N Miami Ave Suite 1, Miami, FL, 33169, USA

    Sherif Hafez

  3. Department of Oral Biology, Augusta University, Augusta, GA, 30912, USA

    Mohamed E. Awad

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  1. Sherif Hafez
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Correspondence to Sherif Hafez.

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The animals were housed at the Augusta University animal care facility, which is approved by the American Association for Accreditation of Laboratory Animal Care. This study was conducted in accordance with the National Institute of Health guidelines for the care and use of animals in research and all protocols were approved by the institutional animal care and use committee.

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Hafez, S., Khan, M.B., Awad, M.E. et al. Short-Term Acute Exercise Preconditioning Reduces Neurovascular Injury After Stroke Through Induced eNOS Activation. Transl. Stroke Res. 11, 851–860 (2020). https://doi.org/10.1007/s12975-019-00767-y

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