Resveratrol ameliorates thoracic blast exposure-induced inflammation, endoplasmic reticulum stress and apoptosis in the brain through the Nrf2/Keap1 and NF-κB signaling pathway

Blast injuries include the various types of internal and external trauma caused by the impact force of high-speed blast waves with multiple mechanisms involved. Thoracic blast exposure could induce neurotrauma as well, but effective therapies are lacking. Resveratrol is a polyphenol flavonoid secreted by plants and has been shown to provide cardiovascular protection and play anti-inflammatory, antioxidation and anti-cancer roles. However, the effects of resveratrol on thoracic blast exposure-induced brain injury have not been investigated. To explore this, a mouse model of thoracic blast exposureinduced brain injury was established. Sixty C57BL/6 wild type mice were randomly divided equally into four groups (one control group, one model group, and model groups with 25 or 50 mg/kg resveratrol injected intraperitoneally). As traumatic brain injury often accompanied by mental symptoms, cognitive dysfunction and anxious behavior were evaluated by Y maze, elevated plus maze and open field test. We also examined the mice for histopathological changes by hematoxylin-eosin staining; the expressions of inflammatory-related factors by ELISA; endoplasmic reticulum stress in brain tissue via the generation of reactive oxygen species (ROS) and the expressions of inositol-requiring enzyme-alpha (IRE-alpha) and C/EBP homologous protein (CHOP); apoptosis by measuring levels of Bax, p53 and Bcl-2. In addition, proteins of related pathways were also studied by western blotting. We found that resveratrol significantly reduced the levels of inflammatory-related factors, including interleukin (IL)-1 beta, IL-4, and high mobility group box protein 1(HMGB1), and increased the level of anti-inflammatory-related factor, IL-10, under thoracic blast exposure (P < 0.05). Cognitive dysfunction and anxious behavior were also ameliorated by resveratrol. In brain tissue, resveratrol significantly attenuated thoracic blast exposure-induced generation of ROS and expressions of IRE-alpha and CHOP, lowered the expressions of Bax and p53, and maintained Bcl-2 expression (P < 0.05). Additionally, resveratrol significantly ameliorated thoracic blast exposure-induced increases of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor (NF)-kappa B and the decrease in nuclear factor erythroid 2-related factor 2(Nrf2) expression in the brain (P < 0.05). Our results indicate that resveratrol has a protective effect on thoracic blast exposure-induced brain injury that is likely mediated through the Nrf2/Keap1 and NF-kappa B signaling pathways. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study revealed that resveratrol has a protective effect on brain injury induced by thoracic blast exposure, reducing inflammation, improving cognitive dysfunction and anxious behavior. Additionally, resveratrol alleviated oxidative stress in brain tissue, decreased apoptosis-related protein expressions, and exerted its effects through the Nrf2/Keap1 and NF-kappa B signaling pathways.