title: Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits.
abstract: OBJECTIVE
  Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits.
  
  
  METHODS
  Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of MCA for 2 h. The blood samples were collected at different time points prior and during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the protein levels of IL-1β, IL-6, IL-10 and TNF-α in the serum and peri-ischemic brain tissues were detected using Western blot and ELISA, respectively. Inflammatory cell infiltration, neuronal apoptosis and neuronal density were measured morphologically. hUCB-MSCs (5 × 10(6)) were iv injected a few minutes after MCAO.
  
  
  RESULTS
  The serum levels of IL-1β, IL-6 and TNF-α were rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC transplantation markedly and progressively suppressed the ischemia-induced increases of serum IL-1β, IL-6 and TNF-α levels within 6 h MCAO-reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which was prevented by hUCB-MSC transplantation. The expression of IL-1β, IL-6, IL-10 and TNF-α in the peri-ischemic brain tissues showed similar changes as in the serum. hUCB-MSC transplantation markedly suppressed the infiltration of inflammatory cells, and increased the neuronal density around the ischemic region. Furthermore, hUCB-MSC transplantation significantly decreased the percentage of apoptosis around the ischemic region.
  
  
  CONCLUSIONS
  hUCB-MSCs transplantation suppresses inflammatory responses and neuronal apoptosis during the early stage focal cerebral ischemia in rabbits.
authors.affiliation: 1] Departments of Neurology, The 105th Hospital of PLA, Hefei 230031, China [2] Clinic College, Anhui Medical University, Hefei 230032, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Departments of Neurology, The 105th Hospital of PLA, Hefei 230031, China.
authors.forename: Ye-ming
authors.initials: YM
authors.lastname: Guan
authors.affiliation: Departments of Neurology, The 105th Hospital of PLA, Hefei 230031, China.
authors.forename: Hai-li
authors.initials: HL
authors.lastname: Huang
authors.affiliation: 1] Departments of Neurology, The 105th Hospital of PLA, Hefei 230031, China [2] Clinic College, Anhui Medical University, Hefei 230032, China.
authors.forename: Qing-song
authors.initials: QS
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
references.citation: Cytotherapy. 2004;6(5):476-86
references.pmid: 15512914
references.citation: Neurosci Lett. 1998 Jul 31;251(3):189-92
references.pmid: 9726375
references.citation: FASEB J. 2006 Feb;20(2):259-68
references.pmid: 16449798
references.citation: Acta Med Okayama. 2012;66(6):429-34
references.pmid: 23254576
references.citation: J Comp Neurol. 2009 Jul 1;515(1):125-44
references.pmid: 19399885
references.citation: Immunol Res. 2008;42(1-3):3-18
references.pmid: 18626576
references.citation: Stroke. 2000 Oct;31(10):2325-9
references.pmid: 11022058
references.citation: Stem Cells. 2005 Apr;23(4):584-93
references.pmid: 15790779
references.citation: J Neuroinflammation. 2013 May 07;10:59
references.pmid: 23651534
references.citation: Mol Ther. 2005 Jan;11(1):96-104
references.pmid: 15585410
references.citation: Vasc Health Risk Manag. 2012;8:569-80
references.pmid: 23091389
references.citation: J Thromb Thrombolysis. 1996;3(1):51-56
references.pmid: 10608037
references.citation: Stroke. 2002 Apr;33(4):982-7
references.pmid: 11935048
references.citation: Cytotherapy. 2008;10(5):469-78
references.pmid: 18608353
references.citation: Neuroreport. 2000 Aug 21;11(12):2759-64
references.pmid: 10976958
references.citation: Stroke. 2001 Jan;32(1):175-83
references.pmid: 11136934
references.citation: J Pharmacol Exp Ther. 2006 Dec;319(3):991-7
references.pmid: 16801453
references.citation: Trends Neurosci. 1999 Sep;22(9):391-7
references.pmid: 10441299
references.citation: J Transl Med. 2009 Nov 17;7:97
references.pmid: 19919699
references.citation: FEBS J. 2009 Jan;276(2):581-93
references.pmid: 19120450
references.citation: Adv Neurol. 1996;71:281-97; discussion 297-300
references.pmid: 8790806
references.citation: Nat Med. 2009 Feb;15(2):192-9
references.pmid: 19169263
references.citation: Stroke. 2009 Mar;40(3 Suppl):S8-12
references.pmid: 19064795
references.citation: Carcinogenesis. 2003 Jun;24(6):1067-75
references.pmid: 12807754
references.citation: Stroke. 2011 Jul;42(7):2045-53
references.pmid: 21566227
references.citation: Stroke. 2001 Apr;32(4):1005-11
references.pmid: 11283404
references.citation: PLoS One. 2011;6(10):e25863
references.pmid: 22031820
references.citation: Brain Res. 2010 Jun 2;1334:65-72
references.pmid: 20353760
references.citation: Neurobiol Dis. 2008 Dec;32(3):486-98
references.pmid: 18930139
references.citation: Acta Pharmacol Sin. 2013 Jan;34(1):1-2
references.pmid: 23262665
references.citation: Crit Rev Immunol. 2001;21(5):427-49
references.pmid: 11942558
references.citation: Stem Cells Dev. 2010 Mar;19(3):351-8
references.pmid: 19296724
references.citation: Stem Cell Res Ther. 2011 Sep 22;2(5):38
references.pmid: 21939558
references.citation: Biorheology. 2001;38(2-3):203-12
references.pmid: 11381175
references.citation: J Cereb Blood Flow Metab. 1999 Aug;19(8):819-34
references.pmid: 10458589