Temporal pattern of C1q deposition after transient focal cerebral ischemia.
Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success.
Mack
William J
WJ
Department of Neurological Surgery, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. wjm32@columbia.edu
Sughrue
Michael E
ME
Ducruet
Andrew F
AF
Mocco
J
J
Sosunov
Sergey A
SA
Hassid
Benjamin G
BG
Silverberg
Joshua Z
JZ
Ten
Vadim S
VS
Pinsky
David J
DJ
Connolly
E Sander
ES
D000818:Animals; D015153:Blotting, Western; D015922:Complement C1q / Q000378:metabolism*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D013997:Time Factors
D015922:Complement C1q