• Diane L Sewell, Brendon Nacewicz, Frances Liu, Sinarack Macvilay, Anna Erdei, John D Lambris, Matyas Sandor, and Zsuzsa Fabry.
• Department of Pathology, University of Wisconsin-Madison, 1300 University Ave, Madison, WI 53706, USA.
• J. Neuroimmunol. 2004 Oct 1; 155 (1-2): 55-63.

AbstractThe role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3-/- or C5-/- mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3-/- mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5-/- mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.Copyright 2004 Elsevier B.V.

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