title: Anti-inflammatory and antiapoptotic effects of mesenchymal stem cells transplantation in rat brain with cerebral ischemia.
abstract: BACKGROUND
  Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage. Nuclear factor-kappa B (NF-κB) is considered to be a key protein complex involved in this cascade of events. The aim of the present study was to clarify the protection mechanism of the mesenchymal stem cells (MSCs).
  
  
  METHODS
  Lewis rats (N = 90) were randomly assigned to three groups: (1) the sham-operated group; (2) the saline group, in which the animals underwent rat transient middle cerebral artery occlusion (tMCAO, for 2 hours) and were treated with saline through the tail vein; and (3) the MSCs group, in which the animals underwent tMCAO (for 2 hours) and were infused with cultured human MSCs (4 × 10(6)/0.4 ml PBS) through the tail vein. At days 1 and 3 post-MSCs infusion, real-time PCR, and Western blot, immunohistochemical analyses were applied for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and P-IKKβ, p53, and B-cell lymphoma 2 (Bcl-2) expression levels.
  
  
  RESULTS
  TNF-α, IL-1β messenger RNA (mRNA) and P-IκB-α, P-IKKβ, p53 protein expression levels were significantly increased in the saline group compared with the sham group. However, IκB-α and Bcl-2 protein expression levels were markedly decreased in the saline group. After injection of BrdU(+) MSCs, the expression levels of TNF-α, IL-1β mRNA and P-IκB-α, P-IKKβ, p53 protein were significantly decreased. Contrary to these findings, IκB-α, Bcl-2 protein expression levels were markedly increased. In addition, we found that infarct area was significantly reduced in MSCs group.
  
  
  CONCLUSIONS
  These results suggest that MSCs' neuroprotection is attributable to its anti-inflammatory and antiapoptotic effect through inhibition of NF-κB.
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China. Electronic address: gunaibing@126.com.
authors.forename: Naibing
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Rao
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Di
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Mingze
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Neurology, The Central Hospital of Xi'an, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase
keywords: Human mesenchymal stem cells; apoptosis; inflammation; nuclear factor-kappa B; rat cerebral ischemia and reperfusion