RapamycintreatmenthasbeenshowntoincreaseautophagyactivityandactivateAktphosphorylation,suppressingapoptosisinseveralmodelsofischemiareperfusioninjury.However,littlehasbeenstudiedontheneuroprotectiveeffectsonspinalcordinjurybyactivatingAktphosphorylation.Wehypothesizedthatbotheffectsofrapamycin,theincreasedautophagyactivityandAktsignaling,wouldcontributetoitsneuroprotectiveproperties.Inthisstudy,acompressivespinalcordinjurymodelofratwascreatedbyananeurysmclipwitha30gclosingforce.Ratmodelswereintraperitoneallyinjectedwithrapamycin1mg/kg,followedbyautophagyinhibitor3-methyladenine2.5mg/kgandAktinhibitorIV1μg/kg.Westernblotassay,immunofluorescencestainingandterminaldeoxynucleotidyltransferase-mediateddUTPnickendlabelingassaywereusedtoobservetheexpressionofneuronalautophagymoleculeBeclin1,apoptosis-relatedmoleculesBcl-2,Bax,cytochromec,caspase-3andAktsignaling.OurresultsdemonstratedthatrapamycininhibitedtheexpressionofmTORininjuredspinalcordtissueandup-regulatedtheexpressionofBeclin1andphosphorylated-Akt.Rapamycinpreventedthedecreaseofbcl-2expressionininjuredspinalcordtissue,reducedBax,cytochromecandcaspase-3expressionlevelsandreducedthenumberofapoptoticneuronsininjuredspinalcordtissue24hoursafterspinalcordinjury.3-MethyladenineandAktinhibitorIVinterventionsuppressedtheexpressionofBeclin-1andphosphorylated-Aktininjuredspinalcordtissueandreducedtheprotectiveeffectofrapamycinonapoptoticneurons.TheaboveresultsindicatethattheneuroprotectiveeffectofrapamycinonspinalcordinjuryratscanbeachievedbyactivatingautophagyandtheAktsignalingpathway.
