Strokeisthethirdleadingcauseofdeathandtheleadingcauseoflong-termdisabilityin adults.Currenttherapeuticstrategiesforstroke,includingthrombolyticdrugs,suchastissue plasminogenactivatoroffergreatpromiseforthetreatment,butcomplimentaryneuropro- tectivetreatmentsarelikelytoprovideabetteroutcome.Tocounteracttheischemicbrain injuryinmice,anewtherapeuticapproachhasbeenemployedbyusingpalmitoylethano- lamide(PEA).PEAisoneofthemembersofN-acyl-ethanolaminefamilymaintainnotonly redoxbalancebutalsoinhibitthemechanismsofsecondaryinjuryonischemicbraininjury. Treatmentofthemiddlecerebralarteryocclusion(MCAo)-inducedanimalswithPEAreduced edemaandbraininfractionsasevidencedbydecreased2,3,5-triphenyltetrazoliumchloride (TTC)stainingacrossbrainsections.PEA-mediatedimprovementsintissueshistologyshown byreductionoflesionsizeandimprovementinapoptosislevel(assayedbyBaxandBcl-2) furthersupporttheefficacyofPEAtherapy.WedemonstratedthatPEAtreatmentblocked infiltrationofastrocytesandrestoredMCAo-mediatedreducedexpressionofPAR,nitrotyr- osine,iNOS,chymase,tryptase,growthfactors(BDNFandGDNF)andGFAP.PEAalsoinhibited theMCAo-mediatedincreasedexpressionofpJNK,NF-kB,anddegradationofIkB-a. PEA- treatedinjuredanimalsimprovedneurobehavioralfunctionsasevaluatedbymotordeficits. BasedonthesefindingsweproposethatPEAwouldbeusefulinloweringtheriskofdamage orimprovingfunctioninischemia–reperfusionbraininjury-relateddisorders.
Reduction of ischemic brain injury by administration of palmitoylethanolamide after transient middle cerebral artery occlusion in rats.
GENOVESE, TIZIANA;IMPELLIZZERI, DANIELA;CRUPI, ROSALIA;MARINO, Angela;ESPOSITO, EMANUELA;CUZZOCREA, Salvatore
2012-01-01
Abstract
Strokeisthethirdleadingcauseofdeathandtheleadingcauseoflong-termdisabilityin adults.Currenttherapeuticstrategiesforstroke,includingthrombolyticdrugs,suchastissue plasminogenactivatoroffergreatpromiseforthetreatment,butcomplimentaryneuropro- tectivetreatmentsarelikelytoprovideabetteroutcome.Tocounteracttheischemicbrain injuryinmice,anewtherapeuticapproachhasbeenemployedbyusingpalmitoylethano- lamide(PEA).PEAisoneofthemembersofN-acyl-ethanolaminefamilymaintainnotonly redoxbalancebutalsoinhibitthemechanismsofsecondaryinjuryonischemicbraininjury. Treatmentofthemiddlecerebralarteryocclusion(MCAo)-inducedanimalswithPEAreduced edemaandbraininfractionsasevidencedbydecreased2,3,5-triphenyltetrazoliumchloride (TTC)stainingacrossbrainsections.PEA-mediatedimprovementsintissueshistologyshown byreductionoflesionsizeandimprovementinapoptosislevel(assayedbyBaxandBcl-2) furthersupporttheefficacyofPEAtherapy.WedemonstratedthatPEAtreatmentblocked infiltrationofastrocytesandrestoredMCAo-mediatedreducedexpressionofPAR,nitrotyr- osine,iNOS,chymase,tryptase,growthfactors(BDNFandGDNF)andGFAP.PEAalsoinhibited theMCAo-mediatedincreasedexpressionofpJNK,NF-kB,anddegradationofIkB-a. PEA- treatedinjuredanimalsimprovedneurobehavioralfunctionsasevaluatedbymotordeficits. BasedonthesefindingsweproposethatPEAwouldbeusefulinloweringtheriskofdamage orimprovingfunctioninischemia–reperfusionbraininjury-relateddisorders.Pubblicazioni consigliate
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