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In this study we used orally active C5a receptor antagonists (PMX53 and PMX205) developed in our laboratories in a rat model of 3\u2010nitropropionic acid (3\u2010NP) \u2010induced Huntington's disease. Administration of the C5a antagonists (10 mg\/kg\/day, oral) either 48 h pre\u2010 or 48 h post\u2010toxin significantly reduced body weight loss, anorexia, and behavioral and motor deficits associated with 3\u2010NP intoxication. Striatal lesion size, apoptosis, neutrophil infiltration, and hemorrhage were also significantly reduced in C5a antagonist\u2010treated rats. Immunohistochemical analysis demonstrated marked deposition of C3 and C9, and upregulation of C5a receptors on neuronal cells at the time of lesion formation. Inhibition of prostaglandins or TNF\u2010\u03b1 with ibuprofen or infliximab had no effect in this model. The C5a antagonists did not affect 3\u2010NP\u2010induced cell death when added directly to rat striatal neuronal cultures, indicating a secondary mechanism of action\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Our findings demonstrate for the first time that complement activation in the brain, particularly C5a, is a key event in the pathogenesis of this disease model, and suggest a future role for inhibitors of C5a in the treatment of neurodegenerative diseases.\u2014Woodruff, T. M., Crane, J. W., Proctor, L. M., Buller, K. M., Shek, A. B., de Vos, K., Pollitt, S., Williams, H. M., Shiels, I. A., Monk, P. N., Taylor, S. M. Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 1407\u20131417 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-5814com","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T18:17:00Z","timestamp":1151691420000},"page":"1407-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration"],"prefix":"10.1096","volume":"20","author":[{"given":"Trent M.","family":"Woodruff","sequence":"first","affiliation":[{"name":"Promics Ltd., The University of Queensland  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Crane","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, The University of Queensland  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