Brain repair by hematopoietic growth factors in a rat model of stroke

LR Zhao, S Singhal, WM Duan, J Mehta, JA Kessler - Stroke, 2007 - Am Heart Assoc
LR Zhao, S Singhal, WM Duan, J Mehta, JA Kessler
Stroke, 2007Am Heart Assoc
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 …
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.
Am Heart Assoc