{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:49:06Z","timestamp":1787312946189,"version":"build-2736575974"},"reference-count":110,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T00:00:00Z","timestamp":1603497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C4004912"],"award-info":[{"award-number":["NRF-2019R1A2C4004912"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brain Research Program through the NRF","award":["NRF-2017M3C7A1028937"],"award-info":[{"award-number":["NRF-2017M3C7A1028937"]}]},{"name":"Brain Research Program through the NRF","award":["NRF-2020R1A2C2008480"],"award-info":[{"award-number":["NRF-2020R1A2C2008480"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg\/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg\/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood\u2013brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.<\/jats:p>","DOI":"10.3390\/ijms21217897","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T02:34:54Z","timestamp":1603679694000},"page":"7897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Transient Receptor Potential Melastatin 7 (TRPM7) Inhibitors Suppress Seizure-Induced Neuron Death by Inhibiting Zinc Neurotoxicity"],"prefix":"10.3390","volume":"21","author":[{"given":"Jeong Hyun","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Ra","family":"Kho","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Ki","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyeon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom Seok","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Sup","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Won","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1528-1167.2011.03121.x","article-title":"Standards for epidemiologic studies and surveillance of epilepsy","volume":"52","author":"Thurman","year":"2011","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE official report: A practical clinical definition of epilepsy","volume":"55","author":"Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/ana.10789","article-title":"Febrile seizures impair memory and cAMP response-element binding protein activation","volume":"54","author":"Chang","year":"2003","journal-title":"Ann. 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