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Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

  • Authors:
    • Xiaoyan Feng
    • Weiwei Ma
    • Jie Zhu
    • Wei Jiao
    • Yuhai Wang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Wuxi Clinical College of Anhui Medical University, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu 214044, P.R. China, Clinical Medicine Five‑Year Program, 11 Class, 2019 Grade, Wannan Medical College, Wuhu, Jiangsu 241002, P.R. China
    Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 661
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    Published online on: July 18, 2021
       https://doi.org/10.3892/mmr.2021.12300
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Abstract

Traumatic brain injury (TBI) is a major public health problem and a major cause of mortality and disability that imposes a substantial economic burden worldwide. Dexmedetomidine (DEX), a highly selective α‑2‑adrenergic receptor agonist that functions as a sedative and analgesic with minimal respiratory depression, has been reported to alleviate early brain injury (EBI) following traumatic brain injury by reducing reactive oxygen species (ROS) production, apoptosis and autophagy. Autophagy is a programmed cell death mechanism that serves a vital role in neuronal cell death following TBI. However, the precise role of autophagy in DEX‑mediated neuroprotection following TBI has not been confirmed. The present study aimed to investigate the neuroprotective effects and potential molecular mechanisms of DEX in TBI‑induced EBI by regulating neural autophagy in a C57BL/6 mouse model. Mortality, the neurological score, brain water content, neuroinflammatory cytokine levels, ROS production, malondialdehyde levels and neuronal death were evaluated by TUNEL staining, Evans blue extravasation, ELISA, analysis of ROS/lipid peroxidation and western blotting. The results showed that DEX treatment markedly increased the survival rate and neurological score, increased neuron survival, decreased the expression of the LC3, Beclin‑1 and NF‑κB proteins, as well as the cytokines IL‑1β, IL‑6 and TNF‑α, which indicated that DEX‑mediated inhibition of autophagy and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of DEX is partly dependent on the ROS/nuclear factor erythroid 2‑related factor 2 signaling pathway. Taken together, the results of the present study indicated that DEX improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and neuroinflammation.
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Spandidos Publications style
Feng X, Ma W, Zhu J, Jiao W and Wang Y: Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway. Mol Med Rep 24: 661, 2021.
APA
Feng, X., Ma, W., Zhu, J., Jiao, W., & Wang, Y. (2021). Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway. Molecular Medicine Reports, 24, 661. https://doi.org/10.3892/mmr.2021.12300
MLA
Feng, X., Ma, W., Zhu, J., Jiao, W., Wang, Y."Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway". Molecular Medicine Reports 24.3 (2021): 661.
Chicago
Feng, X., Ma, W., Zhu, J., Jiao, W., Wang, Y."Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway". Molecular Medicine Reports 24, no. 3 (2021): 661. https://doi.org/10.3892/mmr.2021.12300
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Spandidos Publications style
Feng X, Ma W, Zhu J, Jiao W and Wang Y: Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway. Mol Med Rep 24: 661, 2021.
APA
Feng, X., Ma, W., Zhu, J., Jiao, W., & Wang, Y. (2021). Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway. Molecular Medicine Reports, 24, 661. https://doi.org/10.3892/mmr.2021.12300
MLA
Feng, X., Ma, W., Zhu, J., Jiao, W., Wang, Y."Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway". Molecular Medicine Reports 24.3 (2021): 661.
Chicago
Feng, X., Ma, W., Zhu, J., Jiao, W., Wang, Y."Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway". Molecular Medicine Reports 24, no. 3 (2021): 661. https://doi.org/10.3892/mmr.2021.12300
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