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Recent reports demonstrate novel functions of complement in normal and diseased CNS, such as regulation of neurogenesis and synapse elimination. Here, we examined the role of complement\u2010derived peptide C3a in unilateral hypoxia\u2010ischemia (HI), a model of neonatal HI encephalopathy. HI injury was induced at postnatal day 9 (P9), and loss of hippocampal tissue was determined on P31. We compared WT mice with transgenic mice expressing C3a under the control of glial fibrillary acidic protein promoter, which express biologically active C3a only in CNS and without the requirement of\n                    <jats:italic>a priori<\/jats:italic>\n                    complement activation. Further, we injected C3a peptide into the lateral cerebral ventricle of mice lacking the C3a receptor (C3aR) and WT mice and assessed HI\u2010induced memory impairment 41 d later. We found that HI\u2010induced tissue loss in C3a overexpressing mice was reduced by 50% compared with WT mice. C3a peptide injected 1 h after HI protected WT but not C3aR\u2010deficient mice against HI\u2010induced memory impairment. Thus, C3a acting through its canonical receptor ameliorates behavioral deficits after HI injury, and C3aR is a novel therapeutic target for the treatment of neonatal HI encephalopathy.\u2014J\u00e4rlestedt, K., Rousset, C. I., St\u00e5hlberg, A., Sourkova, H., Atkins, A. L., Thornton, C., Barnum, S. R., Wetsel, R. A., Dragunow, M., Pekny, M., Mallard, C., Hagberg, H., Pekna, M., Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic\u2010ischemic brain injury. FASEB J. 27, 3797\u20133804 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-230011","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T02:44:09Z","timestamp":1370400249000},"page":"3797-3804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic\u2010ischemic brain injury"],"prefix":"10.1096","volume":"27","author":[{"given":"Katarina","family":"J\u00e4rlestedt","sequence":"first","affiliation":[{"name":"Perinatal Center Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine I.","family":"Rousset","sequence":"additional","affiliation":[{"name":"Centre for the 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