title: Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats.
abstract: OBJECTIVE
  This study was designed to follow the effects of bone marrow stromal cell (BMSC) administration in rats after traumatic brain injury (TBI) for a 3-month period.
  
  
  METHODS
  Forty adult female Wistar rats were injured by a controlled cortical impact and, 1 week later, were injected intravenously with one of three different doses of BMSCs (2 x 10(6), 4 x 10(6), or 8 x 10(6) cells per animal) obtained in male rats. Control rats received phosphate-buffered saline (PBS). Neurological function in these rats was studied using a neurological severity scale (NSS). The rats were killed 3 months after injury, and immunohistochemical stains were applied to brain samples to study the distribution of the BMSCs. Additional brain samples were analyzed by quantitative enzyme-linked immunosorbent assays to measure the expression of the growth factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Three months after injury, BMSCs were present in the injured brain and their number was significantly greater in animals that received 4 x 10(6) or 8 x 10(6) BMSCs than in animals that received 2 x 10(6) BMSCs. The cells were primarily distributed around the lesion boundary zone. Functional outcome was significantly better in rats that received 4 x 10(6) or 8 x 10(6) BMSCs, compared with control animals, although no improvement was seen in animals that received 2 x 10(6) BMSCs. All doses of BMSCs significantly increased the expression of BDNF but not that of NGF; however, this increase was significantly larger in animals that received 4 x 10(6) or 8 x 10(6) BMSCs than in controls or animals that received 2 x 10(6) BMSCs.
  
  
  CONCLUSIONS
  In summary, when injected in rats after TBI, BMSCs are present in the brain 3 months later and significantly improve functional outcome.
authors.affiliation: Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA. nsaam@neuro.hfh.edu
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Dunyue
authors.initials: D
authors.lastname: Lu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Anton
authors.initials: A
authors.lastname: Goussev
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D005260:Female; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation*; D016896:Treatment Outcome