IngentaConnect Fast Track Article: Exercise pre-conditioning reduces...rix metalloproteinase-9 activity

Authors: Alecia Curry, Miao Guo, Rohit Patel, Brandon Liebelt, Shane Sprague, Qin Lai, Nathan Zwagerman, Frank X. Cao, David Jimenez, Yuchuan Ding

Abstract:

Objective: We sought to determine whether cerebral inflammation in ischemic rats was reduced by a neuroprotective action of pre-ischemic tumor necrosis factor-α up-regulation, which down-regulated matrix metalloproteinase-9 activity via extracellular signal-regulated kinase 1/2 phosphorylation. Material and methods: 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-α 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. Results: 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-1expression in exercised animals. Exercised animals treated with either tumor necrosis factor-α 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-1expression was not. Neuroprotection remained when the exercised ischemic rats were treated with both UO126 and doxycycline. Conclusion: These results suggest that exercise-induced up-regulation of tumor necrosis factor-α before stroke and extracellular signal-regulated kinase 1/2 phosphorylation play a role in decreasing brain inflammation by regulating matrix metalloproteinase-9 activity.

Exercise pre-conditioning reduces brain inflammation in stroke via tumor necrosis factor-α, extracellular signal-regulated kinase 1/2 and matrix metalloproteinase-9 activity