Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

(整期优先)网络出版时间:2014-12-22
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Therearecurrentlynofederallyapprovedneuroprotectiveagentstotreattraumaticbraininjury.Progesterone,ahydrophobicsteroidhormone,hasbeenshowninrecentstudiestoexhibitneuroprotectiveeffectsincontrolledcorticalimpactratmodels.Aktisaproteinkinaseknowntoplayaroleincellsignalingpathwaysthatreduceedema,inflammation,apoptosis,andpromotecellgrowthinthebrain.ThisstudyaimstodetermineifprogesteronemodulatesthephosphorylationofAktviaitsthreonine308phosphorylationsite.Phosphorylationatthethreonine308siteisoneofseveralsitesresponsibleforactivatingAktandenablingtheproteinkinasetocarryoutitsneuroprotectiveeffects.ToassesstheeffectsofprogesteroneonAktphosphorylation,C57BL/6miceweretreatedwithprogesterone(8mg/kg)at1(intraperitonally),6,24,and48hours(subcutaneously)postclosed-skulltraumaticbraininjury.Thehippocampuswasharvestedat72hourspostinjuryandpreparedforwesternblotanalysis.TraumaticbraininjurycausedasignificantdecreaseinAktphosphorylationcomparedtoshamoperation.However,micetreatedwithprogesteronefollowingtraumaticbraininjuryhadanincreaseinphosphorylationofAktcomparedtotraumaticbraininjuryvehicle.Ourfindingssuggestthatprogesteroneisaviabletreatmentoptionforactivatingneuroprotectivepathwaysaftertraumaticbraininjury.