Protective effect of C5a receptor inhibition after murine reperfused stroke

GH Kim, J Mocco, DK Hahn, CP Kellner… - …, 2008 - journals.lww.com
GH Kim, J Mocco, DK Hahn, CP Kellner, RJ Komotar, AF Ducruet, WJ Mack, ES Connolly Jr
Neurosurgery, 2008journals.lww.com
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 …
Abstract
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.
Lippincott Williams & Wilkins