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Our previous studies have demonstrated that controlled decompression (CDC) surgery attenuates brain injury and reduces the rate of complications after TBI. Here, we investigated the potential molecular mechanisms of CDC in experimental models. The in vitro experiments were performed in a traumatic neuronal injury (TNI) model following compression treatment in primary cultured cortical neurons. We found that compression aggravates TNI\u2010induced neuronal injury, which was significantly attenuated by CDC for 2\u2009h or 3\u2009h. The results of immunocytochemistry showed that CDC reduced neuronal necroptosis and activation of RIP3 induced by TNI and compression, with no effect on RIP1 activity. These protective effects were associated with decreased levels of inflammatory cytokines and preserved intracellular Ca<jats:sup>2+<\/jats:sup> homeostasis. In addition, the expression of the two\u2010pore domain K<jats:sup>+<\/jats:sup> channel TREK\u20101 and its activity was increased by compression and prolonged by CDC. Treatment with the TREK\u20101 blockers, spadin or SID1900, could partially prevent the effects of CDC on intracellular Ca<jats:sup>2+<\/jats:sup> metabolism, necroptosis, and neuronal injury following TNI and compression. Using a traumatic intracranial hypertension model in rats, we found that CDC for 20\u2009min or 30\u2009min was effective in alleviating brain edema and locomotor impairment in vivo. CDC significantly inhibited neuronal necroptosis and neuroinflammation and increased TREK\u20101 activation, and the CDC\u2010induced protection in vivo was attenuated by spadin and SID1900. In summary, CDC is effective in alleviating compressive neuronal injury both in vitro and in vivo, which is associated with the TREK\u20101\u2010mediated attenuation of intracellular Ca<jats:sup>2+<\/jats:sup> overload, neuronal necroptosis, and neuroinflammation.<\/jats:p>","DOI":"10.1155\/2021\/4280951","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T20:20:07Z","timestamp":1636402807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Controlled Decompression Attenuates Compressive Injury following Traumatic Brain Injury via TREK\u20101\u2010Mediated Inhibition of Necroptosis and Neuroinflammation"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-3799","authenticated-orcid":false,"given":"Tao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-7640","authenticated-orcid":false,"given":"Li-Kun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-0315","authenticated-orcid":false,"given":"Yu-Hai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00458"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.4103\/ajns.AJNS_289_18"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/02688697.2016.1159655"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.919796"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00107"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.5137\/1019-5149.jtn.8135-13.1"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.230"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600234"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01077.x"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2117"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00379"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01828-x"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-012-9875-5"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.10.451"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.08.014"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.08.007"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2198-5"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2010.11.015"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-03373-9"},{"key":"e_1_2_11_20_2","first-page":"76","article-title":"New technique for surgical decompression in traumatic brain injury: merging two concepts to prevent early and late complications of unilateral decompressive craniectomy with dural expansion","volume":"10","author":"de Andrade A. 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