{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:54:31Z","timestamp":1791924871071,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Scientific Research Foundation of Guangdong Province","award":["A2019135"],"award-info":[{"award-number":["A2019135"]}]},{"name":"Science and Technology Project of Guangdong Province","award":["2017A020215053"],"award-info":[{"award-number":["2017A020215053"]}]},{"name":"Scientific research project of Guangdong traditional Chinese Medicine Bureau","award":["20201045"],"award-info":[{"award-number":["20201045"]}]},{"name":"Science and Technology Program of Guangzhou","award":["202002030338"],"award-info":[{"award-number":["202002030338"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoxemia is a typical symptom of acute respiratory distress syndrome. To avoid pulmonary morbidity, low\u00a0tidal\u00a0volume ventilation is often applied. The ventilation strategy will certainly cause hypercapnia. This study aimed to explore whether hypercapnia would promote microglial pyroptosis via inhibiting mitophagy in adult rats with hypoxemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cerebral oxygen extraction ratio (CERO<jats:sub>2<\/jats:sub>) and partial pressure of brain tissue oxygen (PbtO<jats:sub>2<\/jats:sub>) in a rat model of hypercapnia\/hypoxemia were assessed. The reactive oxygen species (ROS) production and the expression of LC3\u2010II\/I, p62, caspase\u20101, gasdermin D\u2010N domains (GSDMD\u2010N), IL\u20101\u03b2, and IL\u201018 in microglial cells were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypercapnia decreased the PbtO<jats:sub>2<\/jats:sub> levels of the hypoxic rats, which was further evidenced by the increased levels of CERO<jats:sub>2<\/jats:sub>. Expression levels of LC3\u2010II were reduced, while p62 expression was increased by hypercapnia in hypoxic microglia. Hypercapnia increased the production of ROS and the expression of caspase\u20101, GSDMD\u2010N, IL\u20101\u03b2, and IL\u201018 in hypoxia\u2010activated microglia. Scavenging ROS inhibited microglial pyroptosis and expression of IL\u20101\u03b2 and IL\u201018.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that hypercapnia\u2010induced mitophagy inhibition may promote pyroptosis and enhance IL\u20101\u03b2 and IL\u201018 release in hypoxia\u2010activated microglia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13435","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T06:24:13Z","timestamp":1594794253000},"page":"1134-1146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats"],"prefix":"10.1111","volume":"26","author":[{"given":"Hong\u2010guang","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"School of Medicine South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang\u2010rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao\u2010yun","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010qiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-4199","authenticated-orcid":false,"given":"Hong\u2010ke","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Guangdong Provincial People\u2019s Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-019-0540-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201612-1042OC"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201609-1938OC"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2530-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003406"},{"issue":"342","key":"e_1_2_8_8_1","first-page":"1301","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"18","author":"Brower RG","year":"2000","journal-title":"N Engl J Med"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.11.010"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1051-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-013-1115-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/370530"},{"issue":"10","key":"e_1_2_8_13_1","first-page":"e130624","article-title":"NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes","volume":"6","author":"Gustin A","year":"2015","journal-title":"PLoS One"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.149"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.161"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133328"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.18557.1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01936-3"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18590"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09663"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081386"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.02.012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.025"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1402992"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2015.10.005"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-5229.148655"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01712235"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199422100-00011"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2253-14-87"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0895-5"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1282-6"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2725"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-295X.99.2.195"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90412-H"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.07.002"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051405"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370213489446"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00516"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00216"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181ca8257"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1427-2"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0055-7"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2020.01.006"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.13435","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13435","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.13435","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T19:03:08Z","timestamp":1693854188000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.13435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,14]]},"references-count":44,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/cns.13435"],"URL":"https:\/\/doi.org\/10.1111\/cns.13435","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,14]]},"assertion":[{"value":"2020-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}