{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:23Z","timestamp":1792417403568,"version":"4.4.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFC028"],"award-info":[{"award-number":["2023AFC028"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxic-ischemic brain injury (HIBI) is a major contributor to poor neurological outcomes after cardiac arrest. The complement C5a\u2013C5aR axis has been implicated in ischemic neuronal damage. This study investigated the neuroprotective effects and mechanisms of the C5aR antagonist PMX205 in HIBI. A rat model of HIBI was established via unilateral carotid artery ligation followed by hypoxia. Rats were treated with PMX205 or vehicle. Neurological function, infarct volume, histopathology, oxidative stress, inflammation, and apoptosis were assessed. In vitro, HAPI and HT22 cells were subjected to oxygen-glucose deprivation\/reperfusion (OGD\/R) with PMX205 treatment or C5aR overexpression. PMX205 significantly improved neurological scores, reduced cerebral infarction, and attenuated neuronal damage in the hippocampal CA1 region. PMX205 treatment decreased OGD\/R-induced apoptosis, LDH release, oxidative stress, and pro-inflammatory cytokine production while restoring antioxidant enzyme activity and Bcl-2 expression. C5aR overexpression abolished these neuroprotective effects, confirming mechanism specificity. Furthermore, PMX205 suppressed the upregulation of macrophage migration inhibitory factor (MIF), HIF-1\u03b1, and VEGF induced by hypoxic-ischemic injury. PMX205 confers neuroprotection against HIBI through anti-inflammatory, anti-oxidative, and anti-apoptotic mechanisms dependent on C5aR blockade, highlighting its potential as a therapeutic strategy.<\/jats:p>","DOI":"10.1093\/jnen\/nlag020","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:49:24Z","timestamp":1772023764000},"page":"1249-1260","source":"Crossref","is-referenced-by-count":0,"title":["C5aR antagonism by PMX205 confers neuroprotection in hypoxic-ischemic brain injury models via anti-inflammatory and anti-apoptotic mechanisms"],"prefix":"10.1093","volume":"85","author":[{"given":"Chengjiao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Huanggang Central Hospital of Yangtze University , Huanggang, Hubei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Shang","sequence":"additional","affiliation":[{"name":"Hubei University of Medicine , Shiyan, Hubei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huanggang Central Hospital of Yangtze University , Huanggang, Hubei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huanggang Central Hospital of Yangtze University , Huanggang, Hubei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huanggang Central Hospital of Yangtze University , Huanggang, Hubei,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Gao (\u9ad8\u73ca)","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Huanggang Central Hospital of Yangtze University , 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