title: Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism.
abstract: BACKGROUND
  We sought to investigate the effects of co-grafting neural stem cells (NSCs) with olfactory ensheathing cells (OECs) on neurological behavior in rats subjected to traumatic brain injury (TBI) and explore underlying molecular mechanisms.
  
  
  METHODS
  TBI was established by percussion device made through a weight drop (50 g) from a 30 cm height. Cultured NSCs and OECs isolated from rats were labeled by Hoechst 33342 (blue) and chloromethyl-benzamidodialkyl carbocyanine (CM-Dil) (red), respectively. Then, NSCs and/or OECs, separately or combined, were transplanted into the area surrounding the injury site. Fourteen days after transplantation, neurological severity score (NSS) were recorded. The brain tissue was harvested and processed for immunocytochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Significant neurological function improvement was observed in the three transplant groups, compared to the TBI group, and co-transplantation gave rise to the best improvement. Morphological evaluation showed that the number of neurons in cortex from combination implantation was more than for other groups (P <0.05); conversely, the number of apoptotic cells showed a significant decrease by TUNEL staining. Transplanted NSCs and OECs could survive and migrate in the brain, and the number of neurons differentiating from NSCs in the co-transplantation group was significantly greater than in the NSCs group. At the molecular level, the expressions of IL-6 and BAD in the co-graft group were found to be down regulated significantly, when compared to either the NSC or OEC alone groups.
  
  
  CONCLUSIONS
  The present study demonstrates for the first time the optimal effects of co-grafting NSCs and OECs as a new strategy for the treatment of TBI via an anti-inflammation mechanism.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zou
authors.forename: Visar
authors.initials: V
authors.lastname: Belegu
authors.forename: Long-Yun
authors.initials: LY
authors.lastname: Lv
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.forename: Ting-Yong
authors.initials: TY
authors.lastname: Wang
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Histology, Embryology and Neurobiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China. 193374073@qq.com.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles; D001930:Brain Injuries / Q000628:therapy*; D002232:Carbocyanines; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D009460:Neurologic Examination; D009830:Olfactory Bulb / Q000166:cytology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation*
chemical_list: C434385:3,3'-dioactadecyl-5,5'-di(4-sulfophenyl)oxacarbocyanine; D001562:Benzimidazoles; D002232:Carbocyanines; D016207:Cytokines; D010751:Phosphopyruvate Hydratase; C017807:bisbenzimide ethoxide trihydrochloride