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

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

Research output: Contribution to journalArticle

20 Scopus citations


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-1 expression 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.

Original languageEnglish (US)
Pages (from-to)756-762
Number of pages7
JournalNeurological Research
Issue number7
StatePublished - Sep 1 2010



  • Ischemia reperfusion injury
  • intercellular adhesion molecule
  • leukocyte infiltration
  • matrix metalloproteinase-9

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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