title: NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke.
abstract: Chronic stroke is the phase of brain recovery and repair generally beginning 3 months after stroke onset. No pharmaceutical approach is currently available to enhance brain repair in chronic stroke. We have previously determined the therapeutic effects of stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) alone or in combination (SCF+G-CSF) in an animal model of chronic stroke and demonstrated that only SCF+G-CSF induces long-term functional recovery. However, the mechanism underlying the SCF+G-CSF-induced brain repair in chronic stroke remains largely elusive. In the present study, we determined the role of nuclear factor-kappa B (NF-κB) in neurovascular network remodeling and motor function improvement by SCF+G-CSF treatment in chronic stroke. SCF+G-CSF was subcutaneously administered for 7 days beginning 17 weeks after induction of experimental stroke. To inhibit NF-κB activation, NF-κB inhibitor was infused into the brain before SCF+G-CSF treatment. We observed that NF-κB inhibitor abolished the SCF+G-CSF-induced axonal sprouting, synaptogenesis and angiogenesis in the ipsilesional somatosensorimotor cortex. In addition, blockage of NF-κB activation resulted in elimination of the SCF+G-CSF-induced motor functional restoration in chronic stroke. These data suggest that NF-κB is required for the SCF+G-CSF-induced neuron-vascular network remodeling in the ipsilesional somatosensorimotor cortex and motor functional recovery in chronic stroke.
authors.affiliation: Department of Neurosurgery, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA; Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Louisiana State University Medical School, Shreveport, LA 71130, USA.
authors.forename: Nicolas S
authors.initials: NS
authors.lastname: Duchamp
authors.affiliation: Louisiana State University Medical School, Shreveport, LA 71130, USA.
authors.forename: Dakota J
authors.initials: DJ
authors.lastname: Boston
authors.affiliation: Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Electronic address: ZHAOL@upstate.edu.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D007839:Functional Laterality; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*; D020521:Stroke / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor
keywords: Brain repair; Chronic stroke; G-CSF; Hematopoietic growth factors; NF-κB; SCF