The effect of exercise preconditioning on stroke outcome in ovariectomized mice with permanent middle cerebral artery occlusion

Can J Physiol Pharmacol. 2018 Mar;96(3):287-294. doi: 10.1139/cjpp-2017-0157. Epub 2017 Sep 5.

Abstract

Exercise preconditioning has been shown to be effective in improving behavioral and neuropathological indices after cerebral ischemia. We evaluated the effect of exercise preconditioning, 17β-estradiol, and their combination on stroke outcome using an experimental model of stroke in ovariectomized (OVX) mice. OVX mice were randomly assigned to 4 groups as follows: control (stroke), exercise (exercise and stroke), estradiol (17β-estradiol and stroke), and exercise+estradiol (exercise and 17β-estradiol and stroke). Exercise preconditioning was performed on a treadmill 5 days/week, 40 min/day, at a speed of 18 m/min for 4 weeks. 17β-estradiol was gavaged (40 μg/kg per day) for 4 weeks. Stroke was induced by permanent middle cerebral artery occlusion (pMCAO), and neurological deficits were evaluated 1, 2, and 7 days after stroke. Then, the serum concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10) and infarct volumes were assessed. Exercise preconditioning and 17β-estradiol induced a better outcome compared with the control ischemic mice, which was manifested by decrease in MMP-9, increase in IL-10, diminished infarct volume, and improved neurological deficits. Concomitant administration of 17β-estradiol and exercise also significantly improved these parameters. Exercise preconditioning or administration of 17β-estradiol alone or in combination before pMCAO induced significant neuroprotection in OVX mice.

Keywords: AVC; estradiol; exercise preconditioning; interleukin 10; interleukine 10; matrix metalloproteinase-9; métalloprotéinase matricielle 9; occlusion permanente de l’artère cérébrale moyenne; permanent middle cerebral artery occlusion; préconditionnement par l’exercice physique; stroke.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Estradiol / pharmacology
  • Female
  • Infarction, Middle Cerebral Artery / blood
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Interleukin-10 / blood
  • Matrix Metalloproteinase 9 / blood
  • Mice
  • Ovariectomy*
  • Physical Conditioning, Animal*

Substances

  • Interleukin-10
  • Estradiol
  • Matrix Metalloproteinase 9