Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats

BACKGROUND AND PURPOSE - 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. CONCLUSION - These data provide first evidence that functional restoration in chronic brain ischemia can be attained using hematopoietic growth factors.