Toll-like receptor-4 and cytokine cascade in stroke after exercise

Objectives: 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. Conclusion: 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.