Protective effect of C5a receptor inhibition after murine 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.


CONCLUSIONS
These findings demonstrate that modulation of C5a receptor activity significantly alters the degree of neurological damage after experimental reperfused stroke.
Kim
Grace H
GH
Department of Neurological Surgery, Columbia University, New York, New York 10032, USA. ghkim9@yahoo.com
Mocco
J
J
Hahn
David K
DK
Kellner
Christopher P
CP
Komotar
Ricardo J
RJ
Ducruet
Andrew F
AF
Mack
William J
WJ
Connolly
E Sander
ES
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*
D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a