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Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain Injury in Rats

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Abstract

Increasing evidence has demonstrated that inflammatory response plays a crucial role in the pathogenesis of secondary injury following blast-induced traumatic brain injury (bTBI). Propofol, a lipid-soluble intravenous anesthetic, has been shown to possess therapeutic benefit during neuroinflammation on various brain injury models. Recent findings have proved that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome involved in the process of the inflammatory response following brain trauma, may probably be a promising target in the treatment of bTBI. Rats were randomly divided into six groups (n = 8): normal group; bTBI-12 and 24 h group; bTBI-12 h and bTBI-24 h group treated with propofol; and bTBI treated with control dimethyl sulfoxide (DMSO) group. The effect of propofol on the expression and activation of NLRP3 inflammasome and the degree of oxidative stress and inflammatory cascades, as well as the brain trauma biomarkers were evaluated in rats suffering from bTBI. The enhanced expressions and activation of NLRP3 inflammasome in the cerebral cortex of bTBI rats were substantially suppressed by the administration of propofol, which was paralleled with the decreased oxidative stress, cytokines production, and the amelioration of cerebral cortex damage. Our results have, for the first time, revealed that over-activation of NLRP3 inflammasome in the cerebral cortex may be involved in the process of neuroinflammation during the secondary injury of bTBI in rats. Propofol might relieve the inflammatory response and attenuate brain injury by inhibiting ROS and reluctant depressing NLRP3 inflammasome activation and pro-inflammatory cytokines maturation.

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Acknowledgments

This study was funded by a grant from the National Natural Science Foundation of China (Grant No. 81501658) and Chengdu Military General Hospital Project (Grant No. 2013YG-B033).

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Authors and Affiliations

  1. Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China

    Jie Ma, Wenjing Xiao, Juan Wu, Jiandong Ren, Jun Hou, Kaihua Fan & Botao Yu

  2. Department of Orthopaedics, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610017, People’s Republic of China

    Junrui Wang

  3. Department of Neurosurgery, The 306th Hospital of PLA, NO.9, Anxiang Beili, Deshengmen, Chaoyang District, Beijing, 100101, China

    Jianwen Gu

  4. Department of Neurosurgery, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China

    Jianwen Gu

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  1. Jie Ma
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Correspondence to Jianwen Gu, Kaihua Fan or Botao Yu.

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All procedures that strictly conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health were approved by Institutional Animal Care and Use Committee of Chengdu Military General Hospital.

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The authors declare that they have no conflicts of interest.

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Jie Ma, Wenjing Xiao, and Junrui Wang are co-first authors.

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Ma, J., Xiao, W., Wang, J. et al. Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain Injury in Rats. Inflammation 39, 2094–2103 (2016). https://doi.org/10.1007/s10753-016-0446-8

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