{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:04:51Z","timestamp":1776056691031,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T00:00:00Z","timestamp":1465171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Graduate Student Funding from China Medical University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno\u2010miR\u2010665 regulation. However, the role of rno\u2010miR\u2010665 during the growth spurt of neonatal rodent brains <jats:italic>in\u00a0vivo<\/jats:italic> is still uncertain. Post\u2010natal day 7 (P7) rats received a single injection of propofol 30\u00a0mg\/kg intraperitoneally (<jats:italic>i.p<\/jats:italic>.), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy. The differential expression of rno\u2010miR\u2010665, <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1 (Bcl\u2010xl), and cleaved caspase 3 (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>3) was surveyed by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and western blotting. In addition, the utility of A\u20101155463, a highly potent and <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1\u2010selective antagonist, was aimed to assess the contribution of <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1 for neuroglial survival. Following the intraventricular injection of lentivirus rno\u2010miR\u2010665, neuroprotection was detected by 5\u2010point scale measurement. The single dose of propofol 30\u00a0mg\/kg triggered dose\u2010dependent apoptosis of developing hippocampal astrocytes. Meanwhile, propofol triggered both rno\u2010miR\u2010665 and <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>3, and depressed <jats:italic><jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1<\/jats:italic>, which was predicted as one target gene of rno\u2010miR\u2010665. Combination treatment with A\u20101155463 and propofol induced lower <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels of <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1 and more <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>3 activation than propofol treatment alone <jats:italic>in\u00a0vivo<\/jats:italic>. The lentivirus\u2010mediated knockdown of rno\u2010miR\u2010665 elevated <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1 and attenuated <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>3 levels, whereas up\u2010regulation of rno\u2010miR\u2010665 suppressed <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1 and induced <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>3 expression <jats:italic>in\u00a0vivo<\/jats:italic>. More importantly, rno\u2010miR\u2010665 antagomir infusion improved neurological outcomes of pups receiving propofol during the brain growth spurt. Rno\u2010miR\u2010665, providing a potential target for alternative therapeutics for pediatric anesthesia, is susceptible to propofol by negatively targeting antiapoptotic <jats:italic><jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2L1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13647-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nRelatively little is known about the association between exposure of astrocytes to brief propofol anaesthesia and risk for impairment. Here, it revealed that propofol\u2010related neurotoxicity of neonatal astrocytes was under rno\u2010miR\u2010665 regulation during the brain growth spurt. Rno\u2010miR\u2010665 might act as a clinically alternative therapeutic target for treatment of neurological disorders in peadiatric anesthesia or sedation with propofol in future.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13647","type":"journal-article","created":{"date-parts":[[2016,4,28]],"date-time":"2016-04-28T01:27:03Z","timestamp":1461806823000},"page":"233-242","source":"Crossref","is-referenced-by-count":21,"title":["rno\u2010miR\u2010665 targets <scp>BCL<\/scp>2L1 (Bcl\u2010xl) and increases vulnerability to propofol in developing astrocytes"],"prefix":"10.1111","volume":"138","author":[{"given":"Wen\u2010Chong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Anesthesiology the First Affiliated Hospital China Medical University Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology the First Affiliated Hospital China 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