Exercise-Induced Overexpression of Angiogenic Factors and Reduction of Ischemia / Reperfusion Injury in Stroke

Author(s): Yun-Hong Ding, Xia-Dong Luan, Jie Li, Jose A. Rafols, M. Guthinkonda, Fernando G. Diaz, Yuchuan Ding

Journal Name: Current Neurovascular Research

Volume 1 , Issue 5 , 2004

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The purpose of this study was to determine if exercise could induce expression of vascular endothelial growth factor (VEGF) and angiopoietin 1 and 2, in association with angiogenesis; and if angiogenic changes correlated with reduced brain injury in stroke. Adult male Sprague Dawley rats (3 month old, n=44) were exercised on a treadmill 30 minutes each day for 1, 3 or 6 weeks, or housed as non-exercised controls for 3 weeks. Some 3 week-exercised rats were then housed for an additional 3 weeks. Exercise significantly (p < 0.01) increased mRNA (determined by real-time reverse transcriptase-polymerase chain reaction) expression of angiopoietin 1 and 2 as early as 1 week, with further increases occurring at 3 weeks. A mild increase after 1 week and a robust increase after 3 weeks of exercise in four isoforms (120, 144, 164, 188) of VEGF mRNA levels were significantly (p < 0.01) observed, with VEGF144 being more markedly upregulated. Overexpression of the mRNAs decreased upon withdrawal of exercise. A significant increase (p < 0.01) in the density of microvessels (determined by laminin-immunocytochemistry) was found at 3 weeks of exercise and this continued after exercise was withdrawn. In exercising rats subjected to 2-h MCA occlusion followed by 48-h reperfusion, neurological deficits and infarct volume were significantly reduced. Neuroprotection continued after 3 weeks of rest. This study indicates that pre-ischemic exercise reduces brain injury in stroke. The reduced damage is associated with angiogenesis, possibly induced by angiogenic factors following exercise. Physical exercise up-regulates mRNA levels of the angiopoietin family and VEGF.

Keywords: transient focal cerebral ischemia, treadmill, vascular endothelial growth factor, angiopoietin

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Article Details

Year: 2004
Page: [411 - 420]
Pages: 10
DOI: 10.2174/1567202043361875
Price: $65

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