Searching　for　effective　pharmacological　agents　for　traumatic　brain　injury　(TBI)　treatment　has　largely　been　unsuccessful.　The　transient　receptor　potential　melastatin　7　(TRPM7),　a　TRP　channel　that　is　essential　for　embryonic　development,　has　been　shown　to　mediate　ischemic　neuronal　injury　in　vivo　and　in　vitro,　but　global　deletion　of　TRPM7　in　mice　is　lethal.　Here,　carvacrol　was　used　to　investigate　the　protective　effect　of　TRPM7　inhibition　in　an　in　vitro　traumatic　neuronal　injury　model.　Carvacrol　(0.5　and　1　mM)　reduced　lactate　dehydrogenase　(LDH)　release,　apoptosis　and　caspase-3　activation　after　traumatic　injury　in　cortical　neurons.　These　neuroprotective　effects　were　accompanied　by　alleviated　cytoplasmic　calcium　levels　as　measured　by　calcium　imaging.　In　contrast,　the　thapsigargin　(TG)　induced　store-operated　calcium　entry　(SOCE)　and　the　expression　of　SOCE　related　proteins　in　neurons　were　not　altered　by　carvacrol　treatment.　The　involvement　of　TRPM7　sensitive　calcium　influx　in　our　in　vitro　model　was　confirmed　by　the　results　that　bradykinin　induced　calcium　influx　was　prevented　by　carvacrol　in　neurons.　Furthermore,　carvacrol　significantly　inhibited　the　induction　of　neuronal　nitric　oxide　synthase　(nNOS)　after　traumatic　injury,　and　treatment　with　carvacrol　and　the　nNOS　inhibitor　NLPA　together　had　no　extra　effect　on　calcium　concentration　and　neuronal　injury.　Thus,　inhibition　of　TRPM7　function　by　carvacrol　protects　against　traumatic　neuronal　injury,　and　might　be　a　potential　drug　development　strategy　for　the　treatment　of　TBI.　(C)　2015　Elsevier　Ltd.　All　rights　reserved.