title: Bone Marrow Stromal Cells Promote Neuronal Restoration in Rats with Traumatic Brain Injury: Involvement of GDNF Regulating BAD and BAX Signaling.
abstract: OBJECTIVE
  To investigate the effects of bone marrow stromal cells (BMSCs) and underlying mechanisms in traumatic brain injury (TBI).
  
  
  METHODS
  Cultured BMSCs from green fluorescent protein-transgenic mice were isolated and confirmed. Cultured BMSCs were immediately transplanted into the regions surrounding the injured-brain site to test their function in rat models of TBI. Neurological function was evaluated by a modified neurological severity score on the day before, and on days 7 and 14 after transplantation. After 2 weeks of BMSC transplantation, the brain tissue was harvested and analyzed by microarray assay. And the coronal brain sections were determined by immunohistochemistry with mouse anti-growth-associated protein-43 kDa (anti-GAP-43) and anti-synaptophysin to test the effects of transplanted cells on the axonal regeneration in the host brain. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and Western blot were used to detect the apoptosis and expression of BAX and BAD.
  
  
  RESULTS
  Microarray analysis showed that BMSCs expressed growth factors such as glial cell-line derived neurotrophic factor (GDNF). The cells migrated around the injury sites in rats with TBI. BMSC grafts resulted in an increased number of GAP-43-immunopositive fibers and synaptophysin-positive varicosity, with suppressed apoptosis. Furthermore, BMSC transplantation significantly downregulated the expression of BAX and BAD signaling. Moreover, cultured BMSC transplantation significantly improved rat neurological function and survival.
  
  
  CONCLUSIONS
  Transplanted BMSCs could survive and improve neuronal behavior in rats with TBI. Mechanisms of neuroprotection and regeneration were involved, which could be associated with the GDNF regulating the apoptosis signals through BAX and BAD.
authors.affiliation: Institute of Neuroscience, Faculty of Basic Medicine, Kunming Medical University, Kunming, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.forename: You-Cui
authors.initials: YC
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Hang-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Apiradee
authors.initials: A
authors.lastname: Lim
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000032:analysis / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein