Toll-like receptor-4 and cytokine cascade in stroke after exercise.
OBJECTIVE
As part of the innate immune system, activation of Toll-like receptor-4 by inflammatory mediators causes the release of inflammatory cytokines, leading to cellular damage. Exercise for 3 weeks has been shown to provide neuroprotection against ischemia/reperfusion insults by decreasing inflammation. This study explores the expression of Toll-like receptor-4 in brain parenchyma during an ischemic stroke after exercise, in association with brain injury.


METHODS
Adult male Sprague-Dawley rats were studied in four groups (control, exercise, stroke and stroke after exercise). Exercise consisted of 30 minutes of treadmill running daily for 3 weeks. Using an intraluminal filament, a stroke was induced by 2 hour middle cerebral artery occlusion. Nissl staining was used to determine brain infarct volume. Brain Toll-like receptor-4 messenger RNA expression and protein levels were determined by real time reverse transcriptase polymerase chain reaction and Western blot, respectively.


RESULTS
Exercise significantly (p<0.05) decreased Toll-like receptor-4 messenger RNA and protein expression, in association with significantly (p<0.05) reduced brain infarct volume. The stroke group had significantly (p<0.05) increased levels of Toll-like receptor-4 expression compared to the control, whereas the exercise/stroke group was significantly (p<0.05) attenuated.


CONCLUSIONS
Exercise reduced Toll-like receptor-4 expression within brain tissue in response to ischemia/reperfusion insult. This is the first paper, to our knowledge, indicating the correlation between exercise, Toll-like receptor-4 expression and reduced brain infarct volume.
Zwagerman
Nathan
N
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
Plumlee
Chuck
C
Guthikonda
Murali
M
Ding
Yuchuan
Y
D000818:Animals; D020520:Brain Infarction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005080:Exercise Test / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*
D016207:Cytokines; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4