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(Stroke. 2007;38:2584.)
© 2007 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Li-Ru Zhao, MD, PhD, Departments of Neurology/Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130. 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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