title: Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats.
abstract: BACKGROUND
  The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.
  
  
  METHODS
  Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.
  
  
  RESULTS
  The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).
  
  
  CONCLUSIONS
  ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Chun-Man
authors.initials: CM
authors.lastname: Yuen
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D002452:Cell Count; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D055495:Neurogenesis; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D012333:RNA, Messenger; D014841:von Willebrand Factor; C007293:DAPI