C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage.
Neuroprotective therapy targeting the complement cascade may reduce injury associated with intracerebral hemorrhage (ICH). We investigated the role of C3a-receptor antagonist (C3aRA) after ICH in mice. Autologous whole blood was infused into the right striatum of mice that were treated with C3aRA or vehicle, using both a pre- and postinjury dosing regimen. Hematoma volume, brain water content, and inflammatory cell profile were assessed at 72 h post-ICH. Neurologic dysfunction was assessed by evaluating both spatial memory and sensorimotor capacity. Animals pretreated with C3aRA showed significantly improved neurologic function, brain water content, and granulocyte infiltration relative to vehicle-treated animals when assessed at 72 h. There was no significant difference in hemorrhagic/nonhemorrhagic ratio of microglial activation among all groups. Hematoma volumes were also not significantly different between C3aRA-treated and vehicle-treated animals. Administration of C3aRA beginning 6 h postinjury afforded significant amelioration of neurologic dysfunction as well as a reduction in brain water content. Treatment with C3aRA improved neurologic outcome while reducing inflammatory cell infiltration and brain edema formation after experimental ICH in mice. Results of this study suggest that the C3a receptor may be a promising target for therapeutic intervention in hemorrhagic stroke.
Rynkowski
Michal A
MA
Department of Neurological Surgery, Columbia University, New York, New York 10032, USA.
Kim
Grace H
GH
Garrett
Matthew C
MC
Zacharia
Brad E
BE
Otten
Marc L
ML
Sosunov
Sergei A
SA
Komotar
Ricardo J
RJ
Hassid
Benjamin G
BG
Ducruet
Andrew F
AF
Lambris
John D
JD
Connolly
E Sander
ES
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology*; D006098:Granulocytes; D006406:Hematoma / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011951:Receptors, Complement / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014867:Water / Q000378:metabolism
D018696:Neuroprotective Agents; D011951:Receptors, Complement; C085567:complement C3a receptor; D014867:Water