Published online before print October 12, 2006, doi: 10.1161/01.RES.0000250175.14861.77
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 23, 2006
Revised on September 5, 2006
Accepted on October 3, 2006
Physical Activity Improves Long-Term Stroke Outcome via Endothelial Nitric Oxide Synthase-Dependent Augmentation of Neovascularization and Cerebral Blood Flow
Karen Gertz ;
From the Klinik und Poliklinik für Neurologie (K.G., J.P., G.K., B.W., S.J., M.M., C.H., U.D., M.E.) and Klinik und Poliklinik für Psychiatrie und Psychotherapie (J.P.), Charité Campus Mitte, Berlin; Klinik und Poliklinik für Psychiatrie und Psychotherapie (G.K.), Charité Campus Benjamin Franklin, Berlin; Institut für Pharmakologie (K.B.F.), Universität Bonn; Institut für Physiologie und Pathophysiologie (H.S.), Universität Heidelberg; and Medizinische Klinik und Poliklinik der Universität des Saarlandes (M.B., U.L.), Innere Medizin III, Homburg, Germany.
* To whom correspondence should be addressed. E-mail: matthias.endres{at}charite.de.
Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves endothelium function, and protects from vascular disease. Here, we tested whether voluntary running would enhance neovascularization and long-term recovery following mild brain ischemia. Wild-type mice were exposed to 30 minutes of middle-cerebral artery occlusion (MCAo) and reperfusion. Continuous voluntary running on wheels conferred long-term upregulation of eNOS in the vasculature and of endothelial progenitor cells (EPCs) in the spleen and bone marrow (BM). This was associated with higher numbers of circulating EPCs in the blood and enhanced neovascularization. Moreover, engraftment of TIE2/LacZ-positive BM-derived cells was increased in the ischemic brain. Four weeks after the insult, trained animals showed higher numbers of newly generated cells in vascular sites, increased density of perfused microvessels and sustained augmentation of cerebral blood flow within the ischemic striatum. Moreover, running conferred tissue sparing and improved functional outcome at 4 weeks. The protective effects of running on angiogenesis and outcome were completely abolished when animals were treated with a NOS inhibitor or the antiangiogenic compound endostatin after brain ischemia, and in animals lacking eNOS expression. Voluntary physical activity improves long-term stroke outcome by eNOS-dependent mechanisms related to improved angiogenesis and cerebral blood flow.
Key words: angiogenesis • cerebral ischemia • exercise • nitric oxide synthase
Related Article:
- Protecting the Brain With eNOS: Run for Your Life
- Frank M. Faraci
Circ. Res. 2006 99: 1029-1030.[Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  P. N. Ainslie, J. D. Cotter, K. P. George, S. Lucas, C. Murrell, R. Shave, K. N. Thomas, M. J. A. Williams, and G. Atkinson Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing J. Physiol., August 15, 2008; 586(16): 4005 - 4010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Werner, M. Hanhoun, T. Widmann, A. Kazakov, A. Semenov, J. Poss, J. Bauersachs, T. Thum, M. Pfreundschuh, P. Muller, et al. Effects of Physical Exercise on Myocardial Telomere-Regulating Proteins, Survival Pathways, and Apoptosis J. Am. Coll. Cardiol., August 5, 2008; 52(6): 470 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P.W. Rouhl, R. J. van Oostenbrugge, J. Damoiseaux, J.-W. C. Tervaert, and J. Lodder Endothelial Progenitor Cell Research in Stroke: A Potential Shift in Pathophysiological and Therapeutical Concepts Stroke, July 1, 2008; 39(7): 2158 - 2165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Muller-Ehmsen, D. Braun, T. Schneider, R. Pfister, N. Worm, K. Wielckens, C. Scheid, P. Frommolt, and M. Flesch Decreased number of circulating progenitor cells in obesity: beneficial effects of weight reduction Eur. Heart J., June 2, 2008; 29(12): 1560 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhu, Y. Fan, T. Frenzel, M. Gasmi, R. T. Bartus, W. L. Young, G.-Y. Yang, and Y. Chen Insulin Growth Factor-1 Gene Transfer Enhances Neurovascular Remodeling and Improves Long-Term Stroke Outcome in Mice Stroke, April 1, 2008; 39(4): 1254 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Faraci Protecting the Brain With eNOS: Run for Your Life Circ. Res., November 10, 2006; 99(10): 1029 - 1030. [Full Text] [PDF]
|
|