Document Detail


Exercise pre-conditioning reduces brain inflammation in stroke via tumor necrosis factor-alpha, extracellular signal-regulated kinase 1/2 and matrix metalloproteinase-9 activity.
MedLine Citation:
PMID:  19682410     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alecia Curry; Miao Guo; Rohit Patel; Brandon Liebelt; Shane Sprague; Qin Lai; Nathan Zwagerman; Frank X Cao; David Jimenez; Yuchuan Ding
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-13
Journal Detail:
Title:  Neurological research     Volume:  32     ISSN:  1743-1328     ISO Abbreviation:  Neurol. Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-07     Completed Date:  2011-01-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905298     Medline TA:  Neurol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  756-62     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blotting, Western
Brain / blood supply*,  metabolism,  pathology
Encephalitis / metabolism,  pathology,  therapy*
Intercellular Adhesion Molecule-1 / metabolism
Ischemic Preconditioning / methods*
Male
Matrix Metalloproteinase 9 / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Physical Conditioning, Animal / physiology*
Random Allocation
Rats
Rats, Sprague-Dawley
Stroke / metabolism,  pathology,  therapy*
Tumor Necrosis Factor-alpha / metabolism*
Up-Regulation
Chemical
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 126547-89-5/Intercellular Adhesion Molecule-1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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