Published Online
on September 20, 2004

A more recent version of this article appeared on September 28, 2004

This Article Full Text (PDF) All Versions of this Article: 110/13/1847    most recent 01.CIR.0000142616.07367.66v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shyu, W.-C. Articles by Li, H. Search for Related Content PubMed PubMed Citation Articles by Shyu, W.-C. Articles by Li, H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Stem Cells Related Collections Acute Cerebral Infarction Acute Stroke Syndromes Neuroprotectors Other Stroke Treatment - Medical

Submitted on October 24, 2003
Revised on April 29, 2004
Accepted on May 3, 2004

Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor-Stimulated Stem Cells

Woei-Cherng Shyu MD, PhD, Shinn-Zong Lin MD, PhD, Hui-I Yang BSc, Yi-Shiuan Tzeng MS, Cheng-Yoong Pang PhD, Pao-Sheng Yen MD, and Hung Li PhD^*

From the Department of Neurology, Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien (W.-C.S., S.-Z.L., H.-I.Y., C.-Y.P., P.-S.Y.); Institute of Molecular Biology, Academia Sinica, Taipei (Y.-S.T., H.L.); and Institutes of Biochemistry, National Yang-Ming University, Taipei (H.L.), Taiwan.

^* To whom correspondence should be addressed. E-mail: hungli{at}ccvax.sinica.edu.tw.

Background--Stroke is a leading cause of death and disability worldwide; however, no effective treatment currently exists.

Methods and Results--Rats receiving subcutaneous granulocyte colony-stimulating factor (G-CSF) showed less cerebral infarction, as evaluated by MRI, and improved motor performance after right middle cerebral artery ligation than vehicle-treated control rats. Subcutaneous administration of G-CSF enhanced the availability of circulating hematopoietic stem cells to the brain and their capacity for neurogenesis and angiogenesis in rats with cerebral ischemia.

Conclusions--G-CSF induced increases in bone marrow cell mobilization and targeting to the brain, reducing the volume of cerebral infarction and improving neural plasticity and vascularization.

Key words: granulocyte colony-stimulating factor • neuronal plasticity • stem cells, hematopoietic • stroke

This article has been cited by other articles:

				K. Diederich, S. Sevimli, H. Dorr, E. Kosters, M. Hoppen, L. Lewejohann, R. Klocke, J. Minnerup, S. Knecht, S. Nikol, et al. The Role of Granulocyte-Colony Stimulating Factor (G-CSF) in the Healthy Brain: A Characterization of G-CSF-Deficient Mice J. Neurosci., September 16, 2009; 29(37): 11572 - 11581. [Abstract] [Full Text] [PDF]

				B. T. Bratane, J. Bouley, A. Schneider, B. Bastan, N. Henninger, and M. Fisher Granulocyte-Colony Stimulating Factor Delays PWI/DWI Mismatch Evolution and Reduces Final Infarct Volume in Permanent-Suture and Embolic Focal Cerebral Ischemia Models in the Rat Stroke, September 1, 2009; 40(9): 3102 - 3106. [Abstract] [Full Text] [PDF]

				B. Hochsmann, R. Huber, P. Schauwecker, H. Schrezenmeier, M. Wiesneth, and A. Storch HEMISPHERIC STROKE DOES NOT MOBILIZE CD34+ HEMATOPOIETIC STEM CELLS INTO THE PERIPHERAL BLOOD Neurology, April 7, 2009; 72(14): 1277 - 1278. [Full Text] [PDF]

				A. Oishi, A. Otani, M. Sasahara, H. Kojima, H. Nakamura, Y. Yodoi, and N. Yoshimura Granulocyte Colony-Stimulating Factor Protects Retinal Photoreceptor Cells against Light-Induced Damage Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5629 - 5635. [Abstract] [Full Text] [PDF]

				Z. E. Toth, R. R. Leker, T. Shahar, S. Pastorino, I. Szalayova, B. Asemenew, S. Key, A. Parmelee, B. Mayer, K. Nemeth, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia Blood, June 15, 2008; 111(12): 5544 - 5552. [Abstract] [Full Text] [PDF]

				J. Minnerup, J. Heidrich, J. Wellmann, A. Rogalewski, A. Schneider, and W.-R. Schabitz Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia Stroke, June 1, 2008; 39(6): 1855 - 1861. [Abstract] [Full Text] [PDF]

				H Ince, M Valgimigli, M Petzsch, J S. de Lezo, F Kuethe, S Dunkelmann, G Biondi-Zoccai, and C A Nienaber Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis Heart, May 1, 2008; 94(5): 610 - 616. [Abstract] [Full Text] [PDF]

				W.-C. Shyu, S.-Z. Lin, P.-S. Yen, C.-Y. Su, D.-C. Chen, H.-J. Wang, and H. Li Stromal Cell-Derived Factor-1{alpha} Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 834 - 849. [Abstract] [Full Text] [PDF]

				J. J Ross and C. M Verfaillie Evaluation of neural plasticity in adult stem cells Phil Trans R Soc B, January 12, 2008; 363(1489): 199 - 205. [Abstract] [Full Text] [PDF]

				L.-R. Zhao, H. H. Berra, W.-M. Duan, S. Singhal, J. Mehta, A. V. Apkarian, and J. A. Kessler Beneficial Effects of Hematopoietic Growth Factor Therapy in Chronic Ischemic Stroke in Rats Stroke, October 1, 2007; 38(10): 2804 - 2811. [Abstract] [Full Text] [PDF]

				L.-R. Zhao, S. Singhal, W.-M. Duan, J. Mehta, and J. A. Kessler Brain Repair by Hematopoietic Growth Factors in a Rat Model of Stroke Stroke, September 1, 2007; 38(9): 2584 - 2591. [Abstract] [Full Text] [PDF]

				K.-J. Tsai, Y.-C. Tsai, and C.-K. J. Shen G-CSF rescues the memory impairment of animal models of Alzheimer's disease J. Exp. Med., June 11, 2007; 204(6): 1273 - 1280. [Abstract] [Full Text] [PDF]

				N. Sprigg and P. M.W. Bath Colony Stimulating Factors (Blood Growth Factors) Are Promising but Unproven for Treating Stroke Stroke, June 1, 2007; 38(6): 1997 - 1998. [Full Text] [PDF]

				M. Chopp, Z. G. Zhang, and Q. Jiang Neurogenesis, Angiogenesis, and MRI Indices of Functional Recovery From Stroke Stroke, February 1, 2007; 38(2): 827 - 831. [Abstract] [Full Text] [PDF]

				N. Sprigg, P. M. Bath, L. Zhao, M. R. Willmot, L. J. Gray, M. F. Walker, M. S. Dennis, and N. Russell Granulocyte-Colony-Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke: The Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092) Stroke, December 1, 2006; 37(12): 2979 - 2983. [Abstract] [Full Text] [PDF]

				M. Ogawa, A. C. LaRue, and C. J. Drake Hematopoietic origin of fibroblasts/myofibroblasts: its pathophysiologic implications Blood, November 1, 2006; 108(9): 2893 - 2896. [Abstract] [Full Text] [PDF]

				M. Takamiya, M. Okigaki, D. Jin, S. Takai, Y. Nozawa, Y. Adachi, N. Urao, K. Tateishi, T. Nomura, K. Zen, et al. Granulocyte Colony-Stimulating Factor-Mobilized Circulating c-Kit+/Flk-1+ Progenitor Cells Regenerate Endothelium and Inhibit Neointimal Hyperplasia After Vascular Injury Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 751 - 757. [Abstract] [Full Text] [PDF]

				I. Solaroglu, J. Cahill, V. Jadhav, and J. H. Zhang A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor Stroke, April 1, 2006; 37(4): 1123 - 1128. [Abstract] [Full Text] [PDF]

				W.-C. Shyu, S.-Z. Lin, M.-F. Chiang, C.-Y. Su, and H. Li Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. J. Neurosci., March 29, 2006; 26(13): 3444 - 3453. [Abstract] [Full Text] [PDF]

				W.-C. Shyu, S.-Z. Lin, C.-C. Lee, D. D. Liu, and H. Li Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial Can. Med. Assoc. J., March 28, 2006; 174(7): 927 - 933. [Abstract] [Full Text] [PDF]

				H. Kawada, S. Takizawa, T. Takanashi, Y. Morita, J. Fujita, K. Fukuda, S. Takagi, H. Okano, K. Ando, and T. Hotta Administration of Hematopoietic Cytokines in the Subacute Phase After Cerebral Infarction Is Effective for Functional Recovery Facilitating Proliferation of Intrinsic Neural Stem/Progenitor Cells and Transition of Bone Marrow-Derived Neuronal Cells Circulation, February 7, 2006; 113(5): 701 - 710. [Abstract] [Full Text] [PDF]

				R. L. Zhang, Z. G. Zhang, and M. Chopp Neurogenesis in the Adult Ischemic Brain: Generation, Migration, Survival, and Restorative Therapy Neuroscientist, October 1, 2005; 11(5): 408 - 416. [Abstract] [PDF]

				H. Ince, M. Petzsch, H. D. Kleine, H. Eckard, T. Rehders, D. Burska, S. Kische, M. Freund, and C. A. Nienaber Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction: Final 1-year Results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial Circulation, August 30, 2005; 112(9_suppl): I-73 - I-80. [Abstract] [Full Text] [PDF]

				I. R. Buschmann, K.-A. Hossmann, W.-C. Shyu, S.-Z. Lin, H.-I Yang, C.-Y. Pang, P.-S. Yen, Y.-S. Tzeng, and H. Li Letter Regarding Article by Shyu et al, "Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor-Stimulated Stem Cells" * Response Circulation, May 17, 2005; 111(19): e297 - e298. [Full Text] [PDF]