Exercise Preconditioning Reduces Brain Damage and Inhibits TNF-α Receptor Expression after Hypoxia/Reoxygenation: An In Vivo and In Vitro Study

Author(s): Yun-Hong Ding, Michael Mrizek, Qin Lai, Yimin Wu, Raul Reyes, Jie Li, William W. Davis, Yuchuan Ding.

Journal Name: Current Neurovascular Research

Volume 3 , Issue 4 , 2006

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Abstract:

Exercise reduces ischemia and reperfusion injury in rat stroke models. We investigated whether gradual increases in tumor necrosis factor-α (TNF-α) reported during exercise down-regulates expression of TNF-α receptors I and II (TNFRI and II) in stroke, leading to reduced brain damage. Adult male Sprague Dawley rats were subjected to 30 minutes of exercise on a treadmill each day for 3 weeks. Then, stroke was induced by a 2-hour middle cerebral artery (MCA) occlusion using an intra-luminal filament. Expressions of TNFRI and II mRNA in the brain were detected using a realtime reverse transcriptase-polymerase chain reaction (RT-PCR). Protein expressions of TNFRI and II were determined by enzyme-linked immunoabsorbant assay (ELISA) in serum and brain homogenates. Spatial distribution of TNF-α receptors in brain regions was determined with immunocytochemistry. In human umbilical vein endothelial cells (HUVEC), we addressed the causal effect of TNF-α pretreatment on TNF I and II expression using ELISA and real-time PCR. In exercised rats after stroke, brain infarct was significantly (p < 0.01) reduced in the entire MCA supplied regions, associated with a mild expression of TNFRI and II mRNA and protein. The TNF-α receptors were restricted to the ischemic core. In contrast, a robust expression of TNFRI and II molecules was found in non-exercised rats subjected to similar ischemia/ reperfusion insults. An in vitro study revealed a causal link between TNF-α pretreatment and reduced cellular expression of TNF-α receptors under hypoxic/reoxygenated conditions. Our results suggest that reduced-brain damage in ischemic rats after exercise preconditioning may be attributable to the reduced expression of TNF-α receptors. Chronically increased TNF-α expression was also found to reduce TNFI and II responding to acute ischemia/reperfusion insult.

Keywords: Focal cerebral ischemia, rat, TNF-α signaling pathway, treadmill, reperfusion injury, cell culture

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Article Details

VOLUME: 3
ISSUE: 4
Year: 2006
Page: [263 - 271]
Pages: 9
DOI: 10.2174/156720206778792911
Price: $58

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