QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 15, 2003, 23(28):9459-9468

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (46) Citing Articles via Google Scholar Google Scholar Articles by Cowell, R. M. Articles by Silverstein, F. S. Search for Related Content PubMed PubMed Citation Articles by Cowell, R. M. Articles by Silverstein, F. S.

 Previous Article  |  Next Article 

Cellular/Molecular
Complement Activation Contributes to Hypoxic-Ischemic Brain Injury in Neonatal Rats

Rita M. Cowell,^1,3 Jennifer M. Plane,² and Faye S. Silverstein^1,2,3

Departments of ¹Neurology and ²Pediatrics, and ³Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109

Conflicting data have emerged regarding the role of complement activation in the pathophysiology of cerebral ischemia. On the basis of considerable evidence implicating inflammatory mediators in the progression of neonatal brain injury, we evaluated the contribution of complement activation to cerebral hypoxic-ischemic (HI) injury in the neonatal rat. To elicit unilateral forebrain HI injury, 7-d-old rats underwent right carotid ligation followed by 1.5-2 hr of exposure to 8% oxygen. Using immunoprecipitation and Western blot assays, we determined that HI induces local complement cascade activation as early as 8 hr post-HI; there was an eightfold increase in the activation fragment inactivated C3b at 16 hr. With immunofluorescence assays and confocal microscopy, both C3 and C9 were localized to injured neurons 16 and 24 hr post-HI. To investigate the contribution of systemic complement to brain injury, we administered the complement-depleting agent cobra venom factor (CVF) 24 hr before HI lesioning and evaluated both acute HI-induced complement deposition and the extent of resulting tissue injury 5 d after lesioning. CVF depleted both systemic and brain C3 by the time of surgery and reduced infarct size. Analysis of lesioned, CVF-treated animals demonstrated minimal neuronal C3 deposition but no reduction in C9 deposition. C3-immunoreactive microglia were identified in injured areas. These results indicate that complement activation contributes to HI injury in neonatal rat brain, systemic administration of CVF does not eliminate complement deposition within injured brain, and microglia may represent an important local source of C3 after acute brain injury.

Key words: microglia; endothelium; cobra venom factor; neonatal rat; stroke; C3

---

Received July 7, 2003; revised September 3, 2003; accepted September 4, 2003.

This article has been cited by other articles:

				P. C. Dimayuga, F. H. Y. Cesena, K.-Y. Chyu, J. Yano, A. Amorn, M. C. Fishbein, P. K. Shah, and B. Cercek Natural antibodies and complement modulate intimal thickening after arterial injury Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1593 - R1600. [Abstract] [Full Text] [PDF]

				K. J. Lister and M. J. Hickey Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H694 - H704. [Abstract] [Full Text] [PDF]

				J Mocco, W. J. Mack, A. F. Ducruet, S. A. Sosunov, M. E. Sughrue, B. G. Hassid, M. N. Nair, I. Laufer, R. J. Komotar, M. Claire, et al. Complement Component C3 Mediates Inflammatory Injury Following Focal Cerebral Ischemia Circ. Res., July 21, 2006; 99(2): 209 - 217. [Abstract] [Full Text] [PDF]

				S. A. Back, A. Riddle, and A. R. Hohimer Topical Review: Role of Instrumented Fetal Sheep Preparations in Defining the Pathogenesis of Human Periventricular White-Matter Injury J Child Neurol, July 1, 2006; 21(7): 582 - 589. [Abstract] [PDF]

				V. S. Ten, S. A. Sosunov, S. P. Mazer, R. I. Stark, C. Caspersen, M. E. Sughrue, M. Botto, E. S. Connolly Jr, and D. J. Pinsky C1q-Deficiency Is Neuroprotective Against Hypoxic-Ischemic Brain Injury in Neonatal Mice Stroke, October 1, 2005; 36(10): 2244 - 2250. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help