title: Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-α-induced protein 6.
abstract: OBJECTIVE
  To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms.
  
  
  METHODS
  Adult male SD rats underwent asphxial cardiac arrest to induce global cerebral ischemia, then received intravenous injection of 5×10(6) cultured MSCs of SD rats at 2 h after resuscitation. In another group of cardiac arrest rats, tumor necrosis factor-α-induced protein 6 (TSG-6, 6 μg) was injected into the right lateral ventricle. Functional outcome was assessed at 1, 3, and 7 d after resuscitation. Donor MSCs in the brains were detected at 3 d after resuscitation. The level of serum S-100B and proinflammatory cytokines in cerebral cortex were assayed using ELISA. The expression of TSG-6 and proinflammatory cytokines in cerebral cortex was assayed using RT-PCR. Western blot was performed to determine the levels of TSG-6 and neutrophil elastase in cerebral cortex.
  
  
  RESULTS
  MSCs transplantation significantly reduced serum S-100B level, and improved neurological function after global cerebral ischemia compared to the PBS-treated group. The MSCs injected migrated into the ischemic brains, and were observed mainly in the cerebral cortex. Furthermore, MSCs transplantation significantly increased the expression of TSG-6, and reduced the expression of neutrophil elastase and proinflammatory cytokines in the cerebral cortex. Intracerebroventricular injection of TSG-6 reproduced the beneficial effects of MSCs transplantation in rats with global cerebral ischemia.
  
  
  CONCLUSIONS
  MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia, maybe via upregulation of TSG-6 expression.
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Qing-ming
authors.initials: QM
authors.lastname: Lin
authors.forename: Shen
authors.initials: S
authors.lastname: Zhao
authors.forename: Li-li
authors.initials: LL
authors.lastname: Zhou
authors.forename: Xiang-shao
authors.initials: XS
authors.lastname: Fang
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Zi-tong
authors.initials: ZT
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000473:pathology / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D007275:Injections, Intravenous; D019272:Leukocyte Elastase / Q000235:genetics / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D064568:S100 Calcium Binding Protein beta Subunit; C513056:Tnfaip6 protein, rat; D019272:Leukocyte Elastase