The 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.
Levels of insulin-like growth factors I and II (IGF-I and IGF-II) and somatomedin peptide content (SMPC) were measured in 32 normal term and 11 preterm infants. After acid chromatography to remove somatomedin-binding protein, SMPC was measured by placental membrane radioreceptor assay, while plasma IGF-I and II concentrations were measured by specific RIAs. SMPC levels in term infants were significantly below normal adult levels [0.49 +/- 0.13 (+/- SD) U/ml for infants compared to 1.30 +/- 0.25 U/ml for adult males]. IGF-I levels in term infants were also low, averaging 113 +/- 35 ng/ml for infants; the normal adult levels is 184 +/- 32 ng/ml. The IGF-II level was 282 +/- 84 ng/ml for infants and 687 +/- 169 ng/ml for adults. Both IGF-I and II levels in preterm infants were lower than those in term infants. IGF-I, and IGF-II, and SMPC levels showed a positive correlation with birth weight in term infants. Both IGF-I and IGF-II levels showed a strong positive correlation with gestational age in all infants.
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