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Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats
Rita M Cowell1, Jennifer M Plane, Faye S Silverstein
1Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Summary
Complement activation contributes to neonatal brain injury following hypoxic-ischemic (HI) events. Cobra venom factor (CVF) reduced injury, but microglia may locally source complement components like C3.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Conflicting data exist on complement activation's role in cerebral ischemia.
- Inflammatory mediators are implicated in neonatal brain injury progression.
Purpose of the Study:
- To evaluate complement activation's contribution to cerebral hypoxic-ischemic (HI) injury in neonatal rats.
- To investigate the role of systemic complement depletion using cobra venom factor (CVF).
Main Methods:
- Neonatal rat model of unilateral forebrain HI injury.
- Immunoprecipitation, Western blot, immunofluorescence, and confocal microscopy.
- Complement depletion using cobra venom factor (CVF) prior to HI.
Main Results:
- HI induced local complement cascade activation, with increased C3b fragment 16 hr post-HI.
- C3 and C9 localized to injured neurons 16-24 hr post-HI.
- CVF treatment reduced infarct size and systemic C3 levels, but not C9 deposition; C3-immunoreactive microglia were observed.
Conclusions:
- Complement activation contributes to HI injury in the neonatal rat brain.
- Systemic CVF administration does not fully eliminate complement deposition within the injured brain.
- Microglia may be a significant local source of C3 following acute brain injury.