title: Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice.
abstract: After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord‑injured mice following blockade of ETAR and ETBR. We also examined the post‑traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord‑injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord‑injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long‑term neurological recovery.
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Central Laboratory, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Zhennian
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Yonghuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Orthopaedic Surgery, Ningbo Beilun People Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D044022:Receptor, Endothelin A / Q000235:genetics* / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function; D015398:Signal Transduction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
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