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Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia\u2013ischemia. Only C1q<jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q<jats:sup>\u2212\/\u2212<\/jats:sup>brain mitochondria and preserved activity of the respiratory chain. Compared with C1q<jats:sup>+\/+<\/jats:sup>neurons, cortical C1q<jats:sup>\u2212\/\u2212<\/jats:sup>neurons exhibited resistance to oxygen\u2013glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q<jats:sup>\u2212\/\u2212<\/jats:sup>neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation.<\/jats:p>","DOI":"10.1523\/jneurosci.5249-09.2010","type":"journal-article","created":{"date-parts":[[2010,2,10]],"date-time":"2010-02-10T17:33:24Z","timestamp":1265823204000},"page":"2077-2087","source":"Crossref","is-referenced-by-count":88,"title":["Complement Component C1q Mediates Mitochondria-Driven Oxidative Stress in Neonatal Hypoxic\u2013Ischemic Brain Injury"],"prefix":"10.1523","volume":"30","author":[{"given":"Vadim S.","family":"Ten","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veniamin","family":"Ratner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Sosunov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Botto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baalasubramanian","family":"Sivasankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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