Authors: Bangqing Yuan Fenlan Fu Shaokuan Huang Chuangan Lin Guang Yang Kunlong Ma Hui Shi Zhao Yang
Publish Date: 2016/10/05
Volume: 54, Issue: 8, Pages: 6187-6197
Abstract
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 fibrinogenlike protein 2 Fgl2 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 Fgl2 brain water content and neurological dysfunction Furthermore inhibiting extracellular signalregulated kinase 1/2 ERK1/2 and p38 efficiently inhibited C5amediated Fgl2 production following ICH Taken together these data suggest that C5a/C5aR plays a vital role in the ICHinduced inflammatory damage via Fgl2 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
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