Brain repair by hematopoietic growth factors in a rat model of stroke.
OBJECTIVE
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.
Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. lzhao@lsuhsc.edu
Li-Ru
LR
Zhao
Seema
S
Singhal
Wei-Ming
WM
Duan
Jayesh
J
Mehta
John A
JA
Kessler
D000818:Animals; D001835:Body Weight; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D019089:Stem Cell Factor / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D020521:Stroke / Q000378:metabolism / Q000473:pathology*
D018696:Neuroprotective Agents; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D001973:Bromodeoxyuridine