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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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SCF+G-CSF treatment during chronic stroke increases PSD-95 puncta in the peri-infarct cortex of aged brain 6 weeks after treatment.(A–C) Three-dimensional projection of PSD-95 puncta detected by immunohistochemistry in layer I∼III of the corresponding cortex in the intact controls and the peri-infarct cortex 6 weeks after vehicle treatment or SCF+G-CSF treatment in aged chronic stroke brain. Scale bar, 20 µm. (D) Schematic graph showing where the images were taken. (E) Quantification of PSD-95 puncta (number of PSD-95 puncta per field) in the corresponding cortex of the intact controls and in the peri-infarct cortex of chronic stroke brains in aged mice 6 weeks after treatment. *P<0.05. Intact control, n = 5; stroke+vehicle, n = 5; stroke+S+G, n = 6. Mean ± S.E.M.
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pone-0064684-g005: SCF+G-CSF treatment during chronic stroke increases PSD-95 puncta in the peri-infarct cortex of aged brain 6 weeks after treatment.(A–C) Three-dimensional projection of PSD-95 puncta detected by immunohistochemistry in layer I∼III of the corresponding cortex in the intact controls and the peri-infarct cortex 6 weeks after vehicle treatment or SCF+G-CSF treatment in aged chronic stroke brain. Scale bar, 20 µm. (D) Schematic graph showing where the images were taken. (E) Quantification of PSD-95 puncta (number of PSD-95 puncta per field) in the corresponding cortex of the intact controls and in the peri-infarct cortex of chronic stroke brains in aged mice 6 weeks after treatment. *P<0.05. Intact control, n = 5; stroke+vehicle, n = 5; stroke+S+G, n = 6. Mean ± S.E.M.

Mentions: We then sought to determine whether SCF+G-CSF treatment during chronic stroke enhances the characteristics of synapses in the aged brain. Substantial evidence has supported that PSD-95 plays a critical role in the regulation of excitatory postsynaptic function and strength [23]. We therefore quantified PSD-95 puncta in layer I∼III of the peri-infarct cortex using immunohistochemistry 6 weeks after treatment (Figure 5A–D). Three-dimensional confocal images of PSD-95 positive puncta were analyzed using Image J software. We found that SCF+G-CSF treatment during chronic stroke resulted in a 35% increase in PSD-95 puncta in the peri-infarct cortex of the aged brain when compared to the stroke vehicle group (Figure 5E) (vehicle control vs. SCF+G-CSF: 81.01±6.84 vs. 109.44±7.93, P<0.05). This result provides additional evidence supporting that SCF+G-CSF treatment during chronic stroke increases the formation of synaptic networks in the peri-infarct cortex of aged brain.


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)

SCF+G-CSF treatment during chronic stroke increases PSD-95 puncta in the peri-infarct cortex of aged brain 6 weeks after treatment.(A–C) Three-dimensional projection of PSD-95 puncta detected by immunohistochemistry in layer I∼III of the corresponding cortex in the intact controls and the peri-infarct cortex 6 weeks after vehicle treatment or SCF+G-CSF treatment in aged chronic stroke brain. Scale bar, 20 µm. (D) Schematic graph showing where the images were taken. (E) Quantification of PSD-95 puncta (number of PSD-95 puncta per field) in the corresponding cortex of the intact controls and in the peri-infarct cortex of chronic stroke brains in aged mice 6 weeks after treatment. *P<0.05. Intact control, n = 5; stroke+vehicle, n = 5; stroke+S+G, n = 6. Mean ± S.E.M.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3672166&req=5

pone-0064684-g005: SCF+G-CSF treatment during chronic stroke increases PSD-95 puncta in the peri-infarct cortex of aged brain 6 weeks after treatment.(A–C) Three-dimensional projection of PSD-95 puncta detected by immunohistochemistry in layer I∼III of the corresponding cortex in the intact controls and the peri-infarct cortex 6 weeks after vehicle treatment or SCF+G-CSF treatment in aged chronic stroke brain. Scale bar, 20 µm. (D) Schematic graph showing where the images were taken. (E) Quantification of PSD-95 puncta (number of PSD-95 puncta per field) in the corresponding cortex of the intact controls and in the peri-infarct cortex of chronic stroke brains in aged mice 6 weeks after treatment. *P<0.05. Intact control, n = 5; stroke+vehicle, n = 5; stroke+S+G, n = 6. Mean ± S.E.M.
Mentions: We then sought to determine whether SCF+G-CSF treatment during chronic stroke enhances the characteristics of synapses in the aged brain. Substantial evidence has supported that PSD-95 plays a critical role in the regulation of excitatory postsynaptic function and strength [23]. We therefore quantified PSD-95 puncta in layer I∼III of the peri-infarct cortex using immunohistochemistry 6 weeks after treatment (Figure 5A–D). Three-dimensional confocal images of PSD-95 positive puncta were analyzed using Image J software. We found that SCF+G-CSF treatment during chronic stroke resulted in a 35% increase in PSD-95 puncta in the peri-infarct cortex of the aged brain when compared to the stroke vehicle group (Figure 5E) (vehicle control vs. SCF+G-CSF: 81.01±6.84 vs. 109.44±7.93, P<0.05). This result provides additional evidence supporting that SCF+G-CSF treatment during chronic stroke increases the formation of synaptic networks in the peri-infarct cortex of aged brain.

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