Intracerebral hemorrhage (ICH) is a serious emergency with high mortality and morbidity. Up to date, a limited understanding of ICH pathogenesis is difficult to implement effective therapeutic strategy. Much evidence demonstrates that the complement cascade is activated after experimental ICH. However, the exact mechanism has not been well studied in ICH. In the current study, C57BL/6J mice were injected with autologous whole blood. C5a/C5aR levels, microglia infiltration, inflammatory cytokine, and fibrinogen-like protein 2 (Fgl-2) expression in the perihematomal region were analyzed following ICH. In addition, brain water content and neurological dysfunction were detected following ICH. Our data demonstrated that ICH induced complement activation, along with an increase of C5a/C5aR levels, microglia infiltration, and inflammatory cytokine levels. However, C5aR-/- mice exhibited significant attenuation of inflammatory reaction, accompanied by a remarkable reduction of Fgl-2, brain water content, and neurological dysfunction. Furthermore, inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 efficiently inhibited C5a-mediated Fgl-2 production following ICH. Taken together, these data suggest that C5a/C5aR plays a vital role in the ICH-induced inflammatory damage via Fgl-2, and ERK1/2 and p38 pathways also are involved in the pathogenesis of ICH. Therefore, inhibition of C5a/C5aR activation might enlarge our insights in ICH therapy.
Keywords: C5a/C5aR; Fgl-2; ICH; Inflammatory injury.