{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:50:45Z","timestamp":1789523445108,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271329"],"award-info":[{"award-number":["81271329"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471237"],"award-info":[{"award-number":["81471237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT\/\u03b2\u2010catenin signal pathway. Sprague Dawley (SD) rats aged 1\u00a0day were intraperitoneally injected with lipopolysaccharide (LPS) (1\u00a0mg\/kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7\u00a0days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2<jats:sup>+<\/jats:sup> oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28\u2010day septic rats. The number of PLP<jats:sup>+<\/jats:sup> and MBP<jats:sup>+<\/jats:sup> cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g\u2010ratios were higher. This was coupled with an increase in number of NG2<jats:sup>+<\/jats:sup> cells and decreased number of CC1<jats:sup>+<\/jats:sup> cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7\u00a0days could reverse the above\u2010mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT\/\u03b2\u2010catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a <jats:italic>in vitro<\/jats:italic>. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT\/\u03b2\u2010catenin signaling pathway, which would contribute ultimately to axonal hypomyelination.<\/jats:p>","DOI":"10.1111\/bpa.12798","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T18:35:55Z","timestamp":1571337355000},"page":"495-514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT\/\u03b2\u2010catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide"],"prefix":"10.1111","volume":"30","author":[{"given":"Peixian","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"},{"name":"School of Medicine South China University of Technology Guangzhou 510006 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of critical care medicine Jieyang People's Hospital Jieyang 522000 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"},{"name":"Department of critical care medicine Guangdong Second Provincial General Hospital Guangzhou 510317 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"},{"name":"Affiliated South China Hospital Sourthern Medical University (Guangdong Provincial People's Hospital) Guangzhou 510515 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"},{"name":"Shantou University Medical College Shantou 5105063 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"},{"name":"School of Medicine South China University of Technology Guangzhou 510006 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anatomy Wuhan University School of Basic Medical Sciences Wuhan 430072 Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-7399","authenticated-orcid":false,"given":"Yiyu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Emergency Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080 Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.04.034"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23566"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0153-z"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.10.6341"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37932"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1854-18.2018"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1718-6"},{"key":"e_1_2_11_9_1","first-page":"921","article-title":"Early\u2010onset invasive candidiasis in extremely low birth weight infants: perinatal acquisition predicts poor outcome","volume":"64","author":"Barton M","year":"2017","journal-title":"Clin Infect Dis"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2015.86"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404124200"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.06.001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0570-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23305"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4355"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199905)26:3<201::AID-GLIA2>3.0.CO;2-M"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.014"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00387.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1222"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3803-11.2012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1453-0"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.06.015"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32390-0"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1333-z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808064115"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.01.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2013.09.006"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-019-0389-5"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1110-z"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.101"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059214"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e3181870922"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4787-14.2015"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122912"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0805-x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-017-0020-5"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4258"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2013.10.002"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02217.x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.02.020"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.09180FP"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2010.08.007"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23031"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22932"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041036"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.11.018"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.006"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.031"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2530414"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20170981"},{"key":"e_1_2_11_52_1","first-page":"CD012181","article-title":"Antibiotics at the time of removal of central venous catheter to reduce morbidity and mortality in newborn infants","volume":"3","author":"McMullan RL","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.03.003"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.08.015"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1349-4"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1426-z"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0821-x"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2008.95"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0330-8"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00031-13"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.01.019"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.08.002"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0215-2"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.12656"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0485-y"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22950"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.11.007"},{"key":"e_1_2_11_68_1","first-page":"2871","article-title":"Neonatal maternal separation impairs prefrontal cortical myelination and cognitive functions in rats through activation of wnt signaling","volume":"27","author":"Yang Y","year":"2017","journal-title":"Cereb Cortex"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190722114248"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.052"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10883"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01691"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbpa.12798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.12798","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T19:01:30Z","timestamp":1693854090000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.12798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,6]]},"references-count":71,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/bpa.12798"],"URL":"https:\/\/doi.org\/10.1111\/bpa.12798","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,6]]},"assertion":[{"value":"2019-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}