Stroke, a leading cause of adult disability in the world, is a severe medical condition with limited treatment. Chronic stroke represents the phase beyond 3 months after stroke onset. Physical therapy, the only treatment available for stroke rehabilitation, appears to be effective within 6 months post-stroke. Here we have mechanistically determined the efficacy of combined two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) (SCF+G-CSF) in brain repair 6 months after cortical infarct induction in the transgenic mice carrying yellow fluorescent protein in layer V pyramidal neurons (Thy1-YFP-H). Using a combination of live brain imaging, whole brain imaging, molecular manipulation, synaptic and vascular assessments, and motor function examination, we found that SCF+G-CSF promoted mushroom spine formation, enlarged postsynaptic membrane size, and increased postsynaptic PSD-95 accumulation and blood vessel density in the peri-infarct cavity cortex through NF-κB. Once the SCF+G-CSF-enhanced synaptogenesis and angiogenesis in the peri-infarct cavity cortex were blocked by an NF-κB inhibitor, the SCF+G-CSF-induced motor function improvement was eliminated. These data suggest that a stroke-damaged brain is repairable by SCF+G-CSF even 6 months after the lesion occurs. This study provides novel insights into the development of new restorative strategies for stroke recovery.
This work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS)(R01 NS060911) in the United States.