PMID- 26220904 OWN - NLM STAT- MEDLINE DCOM- 20160920 LR - 20191210 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 90 DP - 2015 Nov TI - Carvacrol attenuates traumatic neuronal injury through store-operated Ca(2+) entry-independent regulation of intracellular Ca(2+) homeostasis. PG - 107-13 LID - S0197-0186(15)30022-X [pii] LID - 10.1016/j.neuint.2015.07.020 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Li, Wen-Tao AU - Li WT AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Zhang, Su-Yuan AU - Zhang SY AD - Library of the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Zhou, Yue-Fei AU - Zhou YF AD - Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. FAU - Zhang, Bin-Fei AU - Zhang BF AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Liang, Zhen-Qiang AU - Liang ZQ AD - Department of Neurosurgery, the Dingxi First People's Hospital, Dingxi, Gansu 743000, China. FAU - Liu, Yong-Hong AU - Liu YH AD - Department of Neurosurgery, the Northwest Civil Aviation Hospital, Xi'an, Shaanxi 710061, China. FAU - Wei, Yan AU - Wei Y AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Li, Chuan-Kun AU - Li CK AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Meng, Xi-Jun AU - Meng XJ AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Xia, Ming AU - Xia M AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Dan, Yong AU - Dan Y AD - Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Song, Jin-Ning AU - Song JN AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150726 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Calcium Channels) RN - 0 (Cymenes) RN - 0 (Monoterpenes) RN - 0 (Neuroprotective Agents) RN - 9B1J4V995Q (carvacrol) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain Injuries/*drug therapy/metabolism MH - Calcium/*metabolism MH - Calcium Channels/*drug effects/metabolism MH - Calcium Signaling/*drug effects MH - Cells, Cultured MH - Cymenes MH - Disease Models, Animal MH - Homeostasis/*drug effects MH - Intracellular Space/drug effects/metabolism MH - Monoterpenes/*pharmacology MH - Neurons/*drug effects/metabolism MH - Neuroprotective Agents/pharmacology MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Calcium homeostasis OT - TRPM7 OT - Traumatic brain injury OT - nNOS EDAT- 2015/07/30 06:00 MHDA- 2016/09/22 06:00 CRDT- 2015/07/30 06:00 PHST- 2015/04/30 00:00 [received] PHST- 2015/07/18 00:00 [revised] PHST- 2015/07/24 00:00 [accepted] PHST- 2015/07/30 06:00 [entrez] PHST- 2015/07/30 06:00 [pubmed] PHST- 2016/09/22 06:00 [medline] AID - S0197-0186(15)30022-X [pii] AID - 10.1016/j.neuint.2015.07.020 [doi] PST - ppublish SO - Neurochem Int. 2015 Nov;90:107-13. doi: 10.1016/j.neuint.2015.07.020. Epub 2015 Jul 26.