title: Protective Effect of Ad-VEGF-Bone Mesenchymal Stem Cells on Cerebral Infarction.
abstract: OBJECTIVE
  To understand the mechanism of intracerebroventricular transplantation of vascular endothelial growth factor (VEGF) genemodified bone mesenchymal stem cells (BMSCs) in rats after cerebral infarction.
  
  
  METHODS
  The middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) model was established in rats using the Zea-Longa suture method. A recombinant adenovirus (Ad-VEGF) was engineered to express VEGF. The rats were divided into 3 groups. Control BMSC infected with control adenovirus (BMSC-Ad), BMSC infected by Ad-VEGF (BMSC-Ad-VEGF), and phosphate buffered saline (PBS) suspension were injected into the intracerebroventricular system of the rats in groups 1, 2 and 3 respectively, 24 hours after middle cerebral artery occlusion (MCAO). The neurological function of rats was evaluated with the modified Neurological Severity Scores (mNSS). The infarct volume of brain in rats was determined using 2,3,5-triphenyltetrazolium chloride (TTC) stain at 14 days. GFAP and pGSK3β expression of ischemic penumbra was determined using immunohistochemical method. GFAP, pAKT, AKT, and pGSK3β expressions were determined with Western blot.
  
  
  RESULTS
  Functional improvement was accelerated in animals receiving BMSC-Ad, while improvement at all times between 7 days and 28 days post MCAO was significantly greater in animals transplanted with BMSC-Ad-VEGF than for other treated animals. The number of GFAP-labeled cells was prevented by post-ischemic BMSC-Ad-VEGF treatment; pMCAO activate the PI3K/AKT/GSK3β pathway to reduce reactive gliosis.
  
  
  CONCLUSIONS
  Our findings demonstrate that PI3K/AKT/GSK3β pathway could reduce reactive gliosis, ameliorate neurological deficit, diminish the percentage of cerebral infarction volume in rats, and facilitate angiogenesis.
authors.affiliation: The Second Hospital Affiliated to Soochow University, Department of Neurosurgery, Soochow, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qiao-Yu
authors.initials: QY
authors.lastname: Li
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D000066829:Neuroprotection / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases