title: Repairing the Brain by SCF+G-CSF Treatment at 6 Months Postexperimental Stroke: Mechanistic Determination of the Causal Link Between Neurovascular Regeneration and Motor Functional Recovery.
abstract: Stroke, a leading cause of adult disability in the world, is a severe medical condition with limited treatment. 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 density-95 accumulation and blood vessel density in the peri-infarct cavity cortex; and that SCF + G-CSF treatment improved motor functional recovery. The SCF + G-CSF-enhanced motor functional recovery was dependent on the synaptic and vascular regeneration in the peri-infarct cavity cortex. 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.
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY, USA Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Lili
authors: L
authors: Cui
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY, USA.
authors: Dandan
authors: D
authors: Wang
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY, USA.
authors: Sandra
authors: S
authors: McGillis
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY, USA.
authors: Michele
authors: M
authors: Kyle
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY, USA Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA ZHAOL@upstate.edu.
authors: Li-Ru
authors: LR
authors: Zhao
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009570:Nitriles / Q000627:therapeutic use; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D012038:Regeneration / Q000187:drug effects*; D013450:Sulfones / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009570:Nitriles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013450:Sulfones; D051996:Transcription Factor RelA; D016179:Granulocyte Colony-Stimulating Factor; D010751:Phosphopyruvate Hydratase
keywords: G-CSF; SCF; brain repair; chronic stroke; hematopoietic growth factors; live brain imaging