Open Access

Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice

  • Authors:
    • Jian Guo
    • Yiqiao Li
    • Zhennian He
    • Bin Zhang
    • Yonghuan Li
    • Jianghua Hu
    • Mingyuan Han
    • Yuanlin Xu
    • Yongfu Li
    • Jie Gu
    • Bo Dai
    • Zhong Chen
  • View Affiliations

  • Published online on: April 22, 2014     https://doi.org/10.3892/ijmm.2014.1751
  • Pages: 74-82
  • Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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 micro­environment 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.

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July 2014
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Copy and paste a formatted citation
APA
Guo, J., Li, Y., He, Z., Zhang, B., Li, Y., Hu, J. ... Chen, Z. (2014). Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice. International Journal of Molecular Medicine, 34, 74-82. https://doi.org/10.3892/ijmm.2014.1751
MLA
Guo, J., Li, Y., He, Z., Zhang, B., Li, Y., Hu, J., Han, M., Xu, Y., Li, Y., Gu, J., Dai, B., Chen, Z."Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice". International Journal of Molecular Medicine 34.1 (2014): 74-82.
Chicago
Guo, J., Li, Y., He, Z., Zhang, B., Li, Y., Hu, J., Han, M., Xu, Y., Li, Y., Gu, J., Dai, B., Chen, Z."Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice". International Journal of Molecular Medicine 34, no. 1 (2014): 74-82. https://doi.org/10.3892/ijmm.2014.1751