title: Reestablishing neuronal networks in the aged brain by stem cell factor and granulocyte-colony stimulating factor in a mouse model of chronic stroke.
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.
authors.affiliation: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, New York, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Sasidhar R
authors.initials: SR
authors.lastname: Murikinati
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Duan
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: Zhao
mesh_terms: D000375:Aging; D000818:Animals; D002908:Chronic Disease; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004347:Drug Interactions; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D051528:Guanylate Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009415:Nerve Net / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019089:Stem Cell Factor / Q000494:pharmacology*; D020521:Stroke / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D051528:Guanylate Kinases