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Published Online
on July 26, 2007

Stroke. 2007
Published online before print July 26, 2007, doi: 10.1161/STROKEAHA.106.476457
A more recent version of this article appeared on September 1, 2007
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Submitted on December 15, 2006
Revised on February 9, 2007
Accepted on March 13, 2007

Brain Repair by Hematopoietic Growth Factors in a Rat Model of Stroke

Li-Ru Zhao MD, PhD*; Seema Singhal MD; Wei-Ming Duan MD, PhD; Jayesh Mehta MD; and John A. Kessler MD

From the Departments of Neurology (L.R.Z., J.A.K.) and Medicine (S.S., J.M.), Northwestern University, Feinberg School of Medicine, Chicago, Ill; and the Departments of Cellular Biology and Anatomy (L.R.Z., W.M.D.) and Neurology (L.R.Z.), Louisiana State University Health Sciences Center, Shreveport, La.

* To whom correspondence should be addressed. E-mail: lzhao{at}lsuhsc.edu.

Background and Purpose—Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are essential growth factors in hematopoiesis. We determined whether receptors for SCF and G-CSF exist in the brain and whether exogenous SCF and G-CSF are beneficial to brain repair after brain ischemia.

Methods—A well-established rat model of experimental stroke was used in this study. SCF, G-CSF, SCF+G-CSF, or saline was subcutaneously administered 3 hours to 7 days after brain ischemia. Bromodeoxyuridine was administered simultaneously. Sensorimotor function was evaluated with a limb placement test and foot fault test over time.

Results—We observed that receptors for SCF and G-CSF were expressed in both neurogenic regions and neurons. SCF-treated rats showed the best functional restoration at 1 week that was maintained 4, 7, and 10 weeks after the final injection. G-CSF-induced functional recovery was limited and unstable. Interestingly, stable but delayed functional improvement was seen in SCF+G-CSF-treated rats. Infarction size was significantly reduced in all growth factor-treated rats. In addition, SCF and SCF+G-CSF enhanced neural progenitor cell proliferation in the subventricular zone bilaterally, whereas G-CSF and SCF+G-CSF treatment increased bromodeoxyuridine -positive cells in periinfarct areas.

Conclusions—SCF and G-CSF are neuroprotective and beneficial to functional restoration when administered during the acute phase after brain ischemia, indicating hematopoietic growth factors play a role in brain repair.


Key words: focal ischemia • functional recovery • hematopoietic growth factor • neural stem cells • treatment




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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]