OBJECTIVE: The complement cascade has been implicated in cerebral ischemia/reperfusion injury. To develop clinically useful therapies that successfully manipulate the complement cascade, the individual roles of its components must be clearly defined. Previous studies have shown that C5 inhibition improves outcome after experimental stroke. In this study, we investigated the role of C5a in stroke injury by inhibiting its activity at the receptor level. METHODS: C5a receptor antagonist or vehicle was administered to mice before temporary middle cerebral artery occlusion. Stroke outcomes were assessed 24 hours later in all mice using both neurological deficit scores and cerebral infarct volumes. RESULTS: Animals treated with C5a receptor antagonist experienced significantly decreased infarct volume and demonstrated an improving trend in neurological function. CONCLUSION: These findings demonstrate that modulation of C5a receptor activity significantly alters the degree of neurological damage after experimental reperfused stroke.
OBJECTIVE: The complement cascade has been implicated in cerebral ischemia/reperfusion injury. To develop clinically useful therapies that successfully manipulate the complement cascade, the individual roles of its components must be clearly defined. Previous studies have shown that C5 inhibition improves outcome after experimental stroke. In this study, we investigated the role of C5a in stroke injury by inhibiting its activity at the receptor level. METHODS:C5a receptor antagonist or vehicle was administered to mice before temporary middle cerebral artery occlusion. Stroke outcomes were assessed 24 hours later in all mice using both neurological deficit scores and cerebral infarct volumes. RESULTS: Animals treated with C5a receptor antagonist experienced significantly decreased infarct volume and demonstrated an improving trend in neurological function. CONCLUSION: These findings demonstrate that modulation of C5a receptor activity significantly alters the degree of neurological damage after experimental reperfused stroke.
Authors: Thiruma V Arumugam; Tim Magnus; Trent M Woodruff; Lavinia M Proctor; Ian A Shiels; Stephen M Taylor Journal: Clin Chim Acta Date: 2006-06-14 Impact factor: 3.786
Authors: Thiruma V Arumugam; Ian A Shiels; Anna J Strachan; Giovani Abbenante; David P Fairlie; Stephen M Taylor Journal: Kidney Int Date: 2003-01 Impact factor: 10.612
Authors: Scott R Barnum; Robert S Ames; Peter R Maycox; Sarah J Hadingham; Jackie Meakin; David Harrison; Andrew A Parsons Journal: Glia Date: 2002-04-15 Impact factor: 7.452
Authors: Brad E Zacharia; Zachary L Hickman; Bartosz T Grobelny; Peter A DeRosa; Andrew F Ducruet; E Sander Connolly Journal: Mediators Inflamm Date: 2010-01-26 Impact factor: 4.711
Authors: Andrew Elvington; Carl Atkinson; Hong Zhu; Jin Yu; Kazue Takahashi; Gregory L Stahl; Mark S Kindy; Stephen Tomlinson Journal: J Immunol Date: 2012-10-01 Impact factor: 5.422
Authors: Andrew F Ducruet; Sergey A Sosunov; Brad E Zacharia; Justin Gorski; Mason L Yeh; Peter Derosa; Gregory Cohen; Paul R Gigante; E Sander Connolly Journal: Transl Stroke Res Date: 2011-08-23 Impact factor: 6.829
Authors: Shiyong Li; Dawei Jiang; Zachary T Rosenkrans; Todd E Barnhart; Emily B Ehlerding; Dalong Ni; Jonathan W Engle; Weibo Cai Journal: Nano Lett Date: 2019-09-13 Impact factor: 11.189
Authors: Paul R Gigante; Ivan S Kotchetkov; Christopher P Kellner; Raqeeb Haque; Andrew F Ducruet; Brian Y Hwang; Robert A Solomon; Eric J Heyer; E Sander Connolly Journal: J Neurol Neurosurg Psychiatry Date: 2010-09-14 Impact factor: 10.154
Authors: Trent M Woodruff; Rahasson R Ager; Andrea J Tenner; Peter G Noakes; Stephen M Taylor Journal: Neuromolecular Med Date: 2009-09-11 Impact factor: 3.843