title: Neuroprotective effects of bone marrow stem cells overexpressing glial cell line-derived neurotrophic factor on rats with intracerebral hemorrhage and neurons exposed to hypoxia/reoxygenation.
abstract: BACKGROUND
  Intracerebral hemorrhage (ICH) represents at least 15% of all strokes in the Western population and a considerably higher proportion at 50% to 60% in the Oriental population.
  
  
  OBJECTIVE
  To investigate whether administration of bone marrow stem cells (BMSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) provides more efficient neuroprotection for rats with ICH and neurons exposed to hypoxia/reoxygenation.
  
  
  METHODS
  Primary rat BMSCs were transfected with rat GDNF gene using virus vector (GDNF/BMSCs) and blank virus plasmid (BVP/BMSCs). Primary rat cortical neurons of rats were exposed to hypoxia and then reoxygenated with GDNF/BMSCs (GDNF/BMSCs group) or BVP/BMSCs (BMSCs group) treatment for 12 hours and 1, 2, 3, and 5 days. Hoechst 33258 staining was used to evaluate apoptosis. GDNF/BMSCs, BVP/BMSCs, and saline (GDNF/BMSCs, BMSCs, and control groups) were injected into the right striatum 3 days after rat ICH induced by injecting collagenase. Modified neurological severity scores and hematoxylin and eosin staining were performed to evaluate neurological function and lesion volume at 1 and 2 weeks after transplantation. Immunostaining was used to observe differentiation of grafted cells (neurofilament-200 for neurons, glial fibrillary acidic protein for astrocytes). The GDNF level and apoptosis were evaluated by Western blotting and terminal deoxynucleotidyl transferase dUTP nick-end labeling, respectively.
  
  
  RESULTS
  The GDNF/BMSCs group had significantly lowered apoptosis compared with the BMSCs group at the given time. The GDNF/BMSCs group had significantly improved functional deficits and reduced lesion volume compared with the BMSCs group. Stable GDNF expression in the GDNF/BMSCs group was detected at the given time in the host brain. The neurofilament-positive grafted cells in the GDNF/BMSCs group were more numerous than in the BMSCs group. The GDNF/BMSCs group had significantly decreased apoptotic cells compared with the BMSCs group.
  
  
  CONCLUSIONS
  These results suggest that GDNF/BMSCs provide better neuroprotection for rats with ICH and neurons exposed to hypoxia/reoxygenation.
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, and Department of Plastic and Reconstructive Surgery, 9th People's Hospital, Shanghai, China.
authors.forename: Chaoxian
authors.initials: C
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Jiangyi
authors.initials: J
authors.lastname: Tu
authors.forename: Hengyun
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Qionglan
authors.initials: Q
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000628:therapy*; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000627:therapeutic use*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D010100:Oxygen