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

Abstract：

OBJECTIVE:We sought to determine whether cerebral inflammation in ischemic rats was reduced by a neuroprotective action of pre-ischemic tumor necrosis factor-alpha 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-alpha 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-alpha 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-1 expression 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-alpha before stroke and extracellular signal-regulated kinase 1/2 phosphorylation play a role in decreasing brain inflammation by regulating matrix metalloproteinase-9 activity.

journal_name

Neurol Res

journal_title

Neurological research

authors

Curry A,Guo M,Patel R,Liebelt B,Sprague S,Lai Q,Zwagerman N,Cao FX,Jimenez D,Ding Y

doi

10.1179/174313209X459101

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

756-62

issue

eissn

0161-6412

issn

1743-1328

pii

ner1970

journal_volume

pub_type

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