Exercise pre-conditioning reduces brain inflammation in stroke via tumor necrosis factor-alpha, extracellular signal-regulated kinase 1/2 and matrix metalloproteinase-9 activity. Neurol Res 2010 Sep;32(7):756-62
Date
08/18/2009Pubmed ID
19682410DOI
10.1179/174313209X459101Scopus ID
2-s2.0-77955644654 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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.
Author List
Curry A, Guo M, Patel R, Liebelt B, Sprague S, Lai Q, Zwagerman N, Cao FX, Jimenez D, Ding YAuthor
Nathan Zwagerman MD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Blotting, Western
Brain
Encephalitis
Intercellular Adhesion Molecule-1
Ischemic Preconditioning
Male
Matrix Metalloproteinase 9
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Physical Conditioning, Animal
Random Allocation
Rats
Rats, Sprague-Dawley
Stroke
Tumor Necrosis Factor-alpha
Up-Regulation
