title: C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage.
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 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.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 40216, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, 350025, Fujian, China.
authors.forename: Fenlan
authors.initials: F
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, 350025, Fujian, China.
authors.forename: Shaokuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, 350025, Fujian, China.
authors.forename: Chuangan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, 350025, Fujian, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 40216, China.
authors.forename: Kunlong
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 40216, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 40216, China. yangzhao5140@sohu.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016207:Cytokines; C490637:Fgl2 protein, mouse; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; D005340:Fibrinogen
keywords: C5a/C5aR; Fgl-2; ICH; Inflammatory injury