title: Neuroprotective Effects of Brain-Derived Neurotrophic Factor and Noggin-Modified Bone Mesenchymal Stem Cells in Focal Cerebral Ischemia in Rats.
abstract: BACKGROUND
  Administration of bone marrow stromal cells (BMSCs) has been reported to ameliorate functional deficits in rat ischemia models. In the present study, we tried to reveal the underlying mechanism of the improvement of neurological function after stroke by BMSCs transfected with brain-derived neurotrophic factor (BDNF) and/or Noggin.
  
  
  METHODS
  BMSCs were transfected with BDNF or/and Noggin using the adenovirus method. Middle cerebral artery occlusion (MCAO) rat models were treated with different types of transfected BMSCs. The treatment effect was assessed by measuring the modified Neurological Severity Score and the expression levels of different stroke-related molecules using Western blot, immunohistochemistry assay (IHC), and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The injection of BDNF or/and Noggin-modified BMSCs could significantly improve the neurological function of MCAO animals. Western blot and IHC staining showed that the expression levels of vascular endothelial growth factor, BCL-2, p-GSK3β, and p-Akt were significantly upregulated, while the expressions of Bax, TLR4, and MyD88 were significantly downregulated. Moreover, ELISA assay revealed that the level of matrix metallopeptidase 9 (MMP-9) and reactive oxygen species were also significantly decreased. These results suggested that the treatment of BDNF or/and Noggin-modified BMSCs may suppress the ischemia-induced apoptosis and inflammation in the model animals, which might be through the Akt/GSK3β and TLR4/MyD88 pathways.
  
  
  CONCLUSIONS
  BDNF or/and Noggin-modified BMSCs may exert neuroprotective effects through the Akt/GSK3β and TLR4/MyD88 pathways. Transplantation of BDNF or/and Noggin-modified BMSCs might be a potential therapeutic method for ischemic stroke in clinics.
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of pediatrics, Institute of Neurology; Tianjin Children's Hospital; No. 225, Tianjin, China.
authors.forename: Xingmiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, Institute of Neurology, General Hospital of Tianjin Medical University, Tianjin, China. Electronic address: chengyan985@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D020780:Matrix Metalloproteinase 9; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D000099176:Noggin Protein
keywords: Akt/GSK3β; Brain-derived neurotrophic factor; Noggin; TLR4/MyD88; bone marrow stromal cells; focal cerebral ischemia; neuroprotection