Abstract
Stroke has a high incidence in the elderly. Stroke enters the chronic phase 3 months after initial stroke onset. Currently, there is no pharmaceutical treatment available for chronic stroke. We have demonstrated the therapeutic effects of the combination of stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) (SCF+G-CSF) on chronic stroke. However, it remains unclear how SCF+G-CSF repairs the brain in chronic stroke. In this study, we determined the effects of SCF+G-CSF on neuronal network remodeling in the aged brain of chronic stroke. Cortical brain ischemia was produced in 16–18 month-old transgenic mice expressing yellow fluorescent protein in layer V pyramidal neurons. SCF+G-CSF was subcutaneously injected for 7 days beginning at 3.5 months post-ischemia. Using both live brain imaging and immunohistochemistry, we observed that SCF+G-CSF increased the mushroom-type spines on the apical dendrites of layer V pyramidal neurons adjacent to the infarct cavities 2 and 6 weeks after treatment. SCF+G-CSF also augmented dendritic branches and post-synaptic density protein 95 puncta in the peri-infarct cortex 6 weeks after treatment. These data suggest that SCF+G-CSF treatment in chronic stroke remodels neural circuits in the aged brain. This study provides evidence to support the development of a new therapeutic strategy for chronic stroke.
Highlights
Stroke is the leading cause of long-term disability in adults worldwide
At week 0, there were no differences in total apical spine density among the groups of the intact controls, stroke vehicle controls, and stroke stem cell factor (SCF)+granulocyte-colony stimulating factor (G-CSF) treatment (Figure 2) (one- way ANOVA: F(2,6) = 2.57, P = 0.16), indicating that the total number of spines in the peri-infarct cortex of the aged brain is not affected in the chronic stroke
In this study we have determined the effects of SCF+G-CSF on neuronal network remodeling in the peri-infarct cortex of the aged brain in chronic stroke
Summary
Stroke is the leading cause of long-term disability in adults worldwide. Most strokes occur in elderly people over age 65 [1]. Based on the pathological progress and timing after stroke onset, a stroke is classified into three phases: acute, subacute and chronic stroke. Both metabolic changes [2] and secondary neuron loss [3] are relatively stable 3 months after stroke onset. 3 months after the stroke onset is considered the chronic phase of stroke. Pharmaceutical treatment for chronic stroke is currently not available
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