{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:47:59Z","timestamp":1791571679446,"version":"4.3.4"},"reference-count":64,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/n\/a","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671165"],"award-info":[{"award-number":["81671165"]}],"id":[{"id":"10.13039\/n\/a","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/n\/a","name":"The Well-Known Physician Project, and the Outstanding Foreign Scientist Workshop in Henan province","doi-asserted-by":"publisher","award":["GZS2024022"],"award-info":[{"award-number":["GZS2024022"]}],"id":[{"id":"10.13039\/n\/a","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The complement cascade contributes to secondary brain injury after intracerebral hemorrhage (ICH). However, research remains scarce on the initiation characteristics of proximal complement pathways and the expression of complement inhibitors in the hemorrhagic brain. In this study, we used collagenase VII-S, thrombin, and hemoglobin injections into mouse brains to establish an ICH model and stimulate the coagulation cascade and hemolysis. Our findings highlighted notable discrepancies in the gene and protein expression profiles of proximal complement components and complement inhibitors within the hemorrhagic brain post ICH. At the mRNA level, the coagulation cascade and hemolysis were linked to potential complement initiation and neuroinflammation via the alternative pathway. In contrast, the hemorrhagic brain showed pronounced upregulation of proteins across all three proximal complement pathways, along with concurrent increases in certain complement inhibitors. If these proximal complement pathways are activated, targeting a single pathway may not be sufficient to inhibit the complement cascade in ICH. To further assess the potential for comprehensive inhibition of the complement cascade, we closely examined the expression of previously identified complement-inhibitory proteins. Our exploration of the distribution and functional roles of CD55, a prominent complement inhibitor, revealed its localization in microglia\/macrophages, neurons, and endothelial cells, but not in astrocytes. Notably, we demonstrated that adeno-associated virus vector-mediated overexpression of CD55 significantly suppressed the complement cascade, mitigated neuroinflammation, and enhanced outcomes following ICH. This study provides previously unrecognized preclinical evidence that warrants further investigation into strategies to inhibit the complement cascade in the hemorrhagic brain.<\/jats:p>","DOI":"10.1042\/cs20250755","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T16:09:37Z","timestamp":1779984577000},"page":"1265-1284","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential activation of proximal complement pathways and therapeutic potential of CD55 overexpression in intracerebral hemorrhage"],"prefix":"10.1042","volume":"140","author":[{"given":"Yinuo","family":"Li","sequence":"first","affiliation":[{"name":"1Department of Neurology, The People\u2019s Hospital of Zhengzhou University & Henan Provincial People\u2019s Hospital, 450003 Zhengzhou, P. R. China"},{"name":"2Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiji","family":"Fu","sequence":"additional","affiliation":[{"name":"1Department of Neurology, The People\u2019s Hospital of Zhengzhou University & Henan Provincial People\u2019s Hospital, 450003 Zhengzhou, P. R. China"},{"name":"2Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Neurology, The People\u2019s Hospital of Zhengzhou University & Henan Provincial People\u2019s Hospital, 450003 Zhengzhou, P. R. China"},{"name":"2Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, P. R. 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