title: Complement C5a is detrimental to histological and functional locomotor recovery after spinal cord injury in mice.
abstract: Based on the studies on the role of complements C3, C1q and factor B, we hypothesized that complement C5a is detrimental to locomotor recovery at the early stage of secondary injury after spinal cord injury (SCI). To test this hypothesis, we investigated the effect of inhibition of complement C5a receptor (C5aR) by using C5aR antagonist PMX53 (C5aRA) and deficiency of complement C5a receptor (C5aR-/- mice) on histological and locomotor recovery after SCI in mice. We demonstrated that the Basso Mouse Scale scores in the mice injected with C5aRA (C5aRA-mice) at 45min before and 24h after SCI and the C5aR-/- mice were markedly higher than those in the mice treated with saline (Saline-mice) and the C5aR+/+ mice respectively between 7 and 28days after SCI. Also, expression of TNF-α and IL-1β in C5aRA-mice was significantly lower than that in Saline-mice from 1 to 24h after SCI. In addition, the percentage of microglia/macrophage in C5aRA mice and C5aR-/- mice was significantly lower than those in their corresponding control groups from 1 to 14days after SCI. Furthermore, C5aRA mice and C5aR-/- mice had less GFAP expression in the injured spinal cord epicenter as compared to Saline mice and C5aR+/+ mice at day 28 after SCI. These findings provided evidence that inhibition or deficiency of C5aR could significantly improve histological and functional locomotor recovery after SCI in mice.
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Xiong
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: zmqian1993@gmail.com.
authors.forename: Zhong Ming
authors.initials: ZM
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Tian-zhi
authors.initials: TZ
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Sengli
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address: yake@cuhk.edu.hk.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Neurosurgery, South-west Hospital, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: jklin@tmmu.edu.cn.
authors.forename: Jiangkai
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); C000591759:C5ar1 protein, mouse; D002491:Central Nervous System Agents; D005904:Glial Fibrillary Acidic Protein; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; D014409:Tumor Necrosis Factor-alpha; C528900:glial fibrillary astrocytic protein, mouse
keywords: BALB/c C5aR mice (C5aR−/−); Basso mouse scale (BMS); Complement C5a receptor antagonist (C5aRA); Microglia/macrophage; Spinal cord injury (SCI)