title: Pifithrin-α enhances the survival of transplanted neural stem cells in stroke rats by inhibiting p53 nuclear translocation.
abstract: OBJECTIVE
  To examine a novel strategy to enhance the survival of grafted neural stem cells (NSCs) in stroke model.
  
  
  METHODS
  Using a cell counting kit-8 (CCK-8) and TUNEL assay to test the protective effects of p53 inhibitor, pifithrin-α (PFT-α), on oxygen glucose deprivation (OGD) in NSCs. We compared the effects of vehicle + NSCs and FFT-α + NSCs on the efficacy of transplantation in stroke rat model using behavioral analysis, immunohistochemistry, etc.
  
  
  RESULTS
  Pifithrin-α increased viability and decreased apoptosis in NSCs after OGD in vitro. By in vivo studies, we showed that the best recovery of neurological function in the stroke rats and the maximum survival of grafted NSCs were found in the PFT-α + NSCs group. Twelve hours after cell transplantation, p53 was localized to the nuclei of grafted NSCs in the vehicle + NSCs group but was primarily localized to the cytoplasm in the PFT-α + NSCs group. The p53-upregulated modulator of apoptosis (PUMA) was highly expressed among the grafted cells in the vehicle + NSCs group compared with that in the PFT-α + NSCs group.
  
  
  CONCLUSIONS
  Our results indicate that PFT-α enhances the survival of grafted NSCs through the inhibition of p53 translocation into the nucleus.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Lei
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Li
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhong-Fei
authors.initials: ZF
authors.lastname: Hao
authors.forename: Shi-Yue
authors.initials: SY
authors.lastname: Xin
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage*; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003131:Combined Modality Therapy / Q000379:methods; D008297:Male; D058953:Neural Stem Cells / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D014050:Toluene / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D052160:Benzothiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin