Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats.
OBJECTIVE
Stroke is the leading cause of adult disability worldwide. Currently, there is no effective treatment for stroke survivors. Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are the growth factors regulating hematopoiesis. We have previously observed that SCF and G-CSF have neuroprotective and functional effects on acute brain ischemia. In the present study, the beneficial effects of SCF and G-CSF on chronic brain ischemia were determined.


METHODS
SCF, G-CSF, or SCF+G-CSF was administered subcutaneously to rats 3.5 months after induction of ischemic stroke by middle cerebral artery occlusion. Neurological deficits were evaluated by limb placement test and foot fault test over time. Field-evoked potential was performed 19 weeks after treatment. Infarct volume was histologically determined using serial coronal sections.


RESULTS
Significant functional improvement was seen in SCF+G-CSF-treated rats 1, 5, and 17 weeks after injections. SCF alone also improved functional outcome, but it did not show as stable improvement as SCF+G-CSF. No functional benefit was seen in G-CSF-treated rats. Field-evoked potential studies further confirmed the behavioral data that the normal pattern of neuronal activity was reestablished in the lesioned brain of the rats with good functional outcome. Interestingly, infarction volume was also significantly reduced in SCF+G-CSF-treated rats.


CONCLUSIONS
These data provide first evidence that functional restoration in chronic brain ischemia can be attained using hematopoietic growth factors.
Zhao
Li-Ru
LR
Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Ill, USA. lzhao@lsuhsc.edu
Berra
Hector H
HH
Duan
Wei-Ming
WM
Singhal
Seema
S
Mehta
Jayesh
J
Apkarian
A Vania
AV
Kessler
John A
JA
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D020127:Recovery of Function / Q000187:drug effects*; D019089:Stem Cell Factor / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor