title: Carvacrol attenuates traumatic neuronal injury through store-operated Ca(2+) entry-independent regulation of intracellular Ca(2+) homeostasis.
abstract: 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.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Li
authors.affiliation: Library of the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Su-Yuan
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yue-Fei
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Bin-Fei
authors.initials: BF
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, the Dingxi First People's Hospital, Dingxi, Gansu 743000, China.
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, the Northwest Civil Aviation Hospital, Xi'an, Shaanxi 710061, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Chuan-Kun
authors.initials: CK
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dan
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: songjinning_xjtu@163.com.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D000081007:Cymenes; D004195:Disease Models, Animal; D006706:Homeostasis / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
chemical_list: D015220:Calcium Channels; D000081007:Cymenes; D039821:Monoterpenes; D018696:Neuroprotective Agents; C073316:carvacrol; D002118:Calcium
keywords: Calcium homeostasis; TRPM7; Traumatic brain injury; nNOS