Attenuated Inflammatory Response in Aged Mice Brains following Stroke 英文参考文献.docVIP

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Attenuated Inflammatory Response in Aged Mice Brains following Stroke 英文参考文献.doc

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Attenuated Inflammatory Response in Aged Mice Brains following Stroke 英文参考文献

AttenuatedInflammatoryResponseinAgedMiceBrains followingStroke MatthiasW.Sieber1,2,RalfA.Claus2,OttoW.Witte1*,ChristianeFrahm1 1Hans Berger Department of Neurology, Jena University Hospital, Jena, Thuringia, Germany, 2Centre for Sepsis Control and Care, Jena University Hospital, Jena, Thuringia,Germany Abstract Background:Increasedageisamajorriskfactorforstrokeincidence,post-ischemicmortality,andsevereandlong-term disability.Strokeoutcomeisconsiderablyinfluencedbypost-ischemicmechanisms.Wehypothesizedthattheinflammatory responsefollowinganischemicinjuryisalteredinagedorganisms. MethodsandResults:Tothatend,weanalyzedtheexpressionpatternofpro-inflammatorycytokines(TNF,IL-1a,IL-1b ,IL- 6),anti-inflammatorycytokines(IL-10,TGFb1),andchemokines(Mip-1a,MCP-1,RANTES)ofadult(2months)andaged(24 months)mice brains at differentreperfusion times(6h, 12h,24h,2d,7d) followingtransient occlusion of themiddle cerebralartery.Theinfarctsizewasassessedtomonitorpossibleconsequencesofanalteredinflammatoryresponseinaged mice.Ourdatarevealedanincreasedneuro-inflammationwithage.Aboveall,wefoundprofoundage-relatedalterationsin thereactiontostroke.Theresponseofpro-inflammatorycytokines(TNF,andIL-1b)andthelevelofchemokines(Mip-1a, and MCP-1) were strongly diminished in the aged post-ischemic brain tissue. IL-6 showed the strongest age-dependent decreaseinitspost-ischemicexpressionprofile.Anti-inflammatorycytokines(TGFb1,andIL-10)revealednosignificantage dependencyafterischemia.Agedmicebrainstendtodevelopsmallerinfarcts. Conclusion:Theattenuatedinflammatoryresponsetostrokeinagedanimalsmaycontributetotheirsmallerinfarcts.The resultspresentedherehighlighttheimportanceofusingagedanimalstoinvestigateage-associateddiseaseslikestroke, andshouldbeconsideredasamajorprerequisiteinthedevelopmentofage-adjustedtherapeuticinterventions. Citation:SieberMW,ClausRA,WitteOW,FrahmC(2011)AttenuatedInflammatoryResponseinAgedMiceBrainsfollowingStroke.PLoSONE6(10):e26288. doi:10.1371/journal.pone.0026288 Edito