title: Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location.
abstract: OBJECTIVE
  Recent work indicates that transplanted neural stem cells (NSCs) can survive, migrate to the injury site, and facilitate recovery from traumatic brain injury (TBI). The present study manipulated timing and location of NSC transplants following controlled cortical impact injury (CCI) in mice to determine optimal transplant conditions.
  
  
  METHODS
  In Experiment 1 (timing), NSCs (E14.5 mouse) were injected into the host striatum, ipsilateral to the injury, at 2, 7, or 14 days. In Experiment 2 (location), NSCs or vehicle were injected into the mouse striatum (7 days post-CCI) either ipsilateral or contralateral to the injury and cognitive and motor abilities were assessed from weeks 1-8 post-transplant. Histological measures of NSC survival, migration, and differentiation were taken at 6 and 8 weeks post-transplant.
  
  
  RESULTS
  The results demonstrate that: (1) 2-7 days post-injury is the optimal time-range for delivering NSCs; (2) time of transplantation does not affect short-term phenotypic differentiation; (3) transplant location affects survival, migration, phenotype, and functional efficacy; and (4) NSC-mediated functional recovery is not contingent upon NSC migration or phenotypic differentiation.
  
  
  CONCLUSIONS
  These findings provide further support for the idea that mechanisms other than the replacement of damaged neurons or glia, such as NSC-induced increases in protective neurotrophic factors, may be responsible for the functional recovery observed in this model of TBI.
authors.affiliation: Department of Emergency Medicine, Emory University, Atlanta, GA, USA. Deborah.Shear@AMEDD.ARMY.MIL
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Shear
authors.forename: Ciara C
authors.initials: CC
authors.lastname: Tate
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Tate
authors.forename: David R
authors.initials: DR
authors.lastname: Archer
authors.forename: Michelle C
authors.initials: MC
authors.lastname: LaPlaca
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
authors.forename: Gary L
authors.initials: GL
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology* / Q000601:surgery*; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003071:Cognition; D003342:Corpus Striatum / Q000503:physiopathology; D004195:Disease Models, Animal; D007839:Functional Laterality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D058953:Neural Stem Cells / Q000637:transplantation*; D010296:Parietal Lobe / Q000293:injuries / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome