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Reestablishing neuronal networks in the aged brain by stem cell factor and granulocyte-colony stimulating factor in a mouse model of chronic stroke.

Cui L, Murikinati SR, Wang D, Zhang X, Duan WM, Zhao LR - PLoS ONE (2013)

Bottom Line: In this study, we determined the effects of SCF+G-CSF on neuronal network remodeling in the aged brain of chronic stroke.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, New York, USA.

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.

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Related in: MedlinePlus

The effect of SCF+G-CSF on total spine density of the apical dendrites of the layer V pyramidal neurons in the peri-infarct cortex of aged brain in chronic stroke.Live brain imaging in the cortex adjacent to the infarct cavities or the corresponding cortex of intact mice was performed before treatment (week 0), 2 and 6 weeks after treatment. Note that there is no significant difference in total spine density of aged brain in chronic stroke among the intact controls (n = 3), stroke with vehicle treatment (n = 6), and stroke with SCF+G-CSF treatment (n = 6) neither before nor after treatment. Apical spine density: number of spines per 10 µm dendrite length. Mean ± S.E.M.
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pone-0064684-g002: The effect of SCF+G-CSF on total spine density of the apical dendrites of the layer V pyramidal neurons in the peri-infarct cortex of aged brain in chronic stroke.Live brain imaging in the cortex adjacent to the infarct cavities or the corresponding cortex of intact mice was performed before treatment (week 0), 2 and 6 weeks after treatment. Note that there is no significant difference in total spine density of aged brain in chronic stroke among the intact controls (n = 3), stroke with vehicle treatment (n = 6), and stroke with SCF+G-CSF treatment (n = 6) neither before nor after treatment. Apical spine density: number of spines per 10 µm dendrite length. Mean ± S.E.M.

Mentions: To determine the extent to which SCF+G-CSF affects total dendritic spine density in the aged brain during chronic stroke, we imaged and analyzed the layer I apical dendritic spines of layer V pyramidal neurons in the cortex adjacent to the infarct cavity before treatment (week 0), 2 and 6 weeks after treatment in the same mice. At week 0, there were no differences in total apical spine density among the groups of the intact controls, stroke vehicle controls, and stroke SCF+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. After the first scanning at week 0, stroke mice were treated with either SCF+G-CSF or an equal volume of vehicle for 7 days, and the brain was scanned again using a multiphoton microscope at 2 and 6 weeks after the final injection. We found that total spine density did not show significant differences among the groups of intact control, stroke vehicle control and stroke SCF+G-CSF treatment either 2 weeks (one- way ANOVA: F(2,6) = 0.53, P = 0.60) or 6 weeks (one- way ANOVA: F(2,6) = 0.40, P = 0.69) after treatment (Figure 2). In addition, the total spine density was not affected by the interaction between the groups and selected time points, and no significant changes were seen over the period of 6 weeks (two-way ANOVA: F(4,12) = 0.884, P = 0.50) (Figure 2). Furthermore, the temporal changes of total spine density during imaging at each selected-time point did not show significant variation among the 3 groups (data not shown). These data suggest that SCF+G-CSF treatment during chronic stroke does not influence the total spine density.


Reestablishing neuronal networks in the aged brain by stem cell factor and granulocyte-colony stimulating factor in a mouse model of chronic stroke.

Cui L, Murikinati SR, Wang D, Zhang X, Duan WM, Zhao LR - PLoS ONE (2013)

The effect of SCF+G-CSF on total spine density of the apical dendrites of the layer V pyramidal neurons in the peri-infarct cortex of aged brain in chronic stroke.Live brain imaging in the cortex adjacent to the infarct cavities or the corresponding cortex of intact mice was performed before treatment (week 0), 2 and 6 weeks after treatment. Note that there is no significant difference in total spine density of aged brain in chronic stroke among the intact controls (n = 3), stroke with vehicle treatment (n = 6), and stroke with SCF+G-CSF treatment (n = 6) neither before nor after treatment. Apical spine density: number of spines per 10 µm dendrite length. Mean ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672166&req=5

pone-0064684-g002: The effect of SCF+G-CSF on total spine density of the apical dendrites of the layer V pyramidal neurons in the peri-infarct cortex of aged brain in chronic stroke.Live brain imaging in the cortex adjacent to the infarct cavities or the corresponding cortex of intact mice was performed before treatment (week 0), 2 and 6 weeks after treatment. Note that there is no significant difference in total spine density of aged brain in chronic stroke among the intact controls (n = 3), stroke with vehicle treatment (n = 6), and stroke with SCF+G-CSF treatment (n = 6) neither before nor after treatment. Apical spine density: number of spines per 10 µm dendrite length. Mean ± S.E.M.
Mentions: To determine the extent to which SCF+G-CSF affects total dendritic spine density in the aged brain during chronic stroke, we imaged and analyzed the layer I apical dendritic spines of layer V pyramidal neurons in the cortex adjacent to the infarct cavity before treatment (week 0), 2 and 6 weeks after treatment in the same mice. At week 0, there were no differences in total apical spine density among the groups of the intact controls, stroke vehicle controls, and stroke SCF+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. After the first scanning at week 0, stroke mice were treated with either SCF+G-CSF or an equal volume of vehicle for 7 days, and the brain was scanned again using a multiphoton microscope at 2 and 6 weeks after the final injection. We found that total spine density did not show significant differences among the groups of intact control, stroke vehicle control and stroke SCF+G-CSF treatment either 2 weeks (one- way ANOVA: F(2,6) = 0.53, P = 0.60) or 6 weeks (one- way ANOVA: F(2,6) = 0.40, P = 0.69) after treatment (Figure 2). In addition, the total spine density was not affected by the interaction between the groups and selected time points, and no significant changes were seen over the period of 6 weeks (two-way ANOVA: F(4,12) = 0.884, P = 0.50) (Figure 2). Furthermore, the temporal changes of total spine density during imaging at each selected-time point did not show significant variation among the 3 groups (data not shown). These data suggest that SCF+G-CSF treatment during chronic stroke does not influence the total spine density.

Bottom Line: In this study, we determined the effects of SCF+G-CSF on neuronal network remodeling in the aged brain of chronic stroke.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, New York, USA.

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.

Show MeSH
Related in: MedlinePlus