Open Access

Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury

  • Authors:
    • Yan Feng
    • Ying Cui
    • Jun-Ling Gao
    • Ming-Hang Li
    • Ran Li
    • Xiao-Hua Jiang
    • Yan-Xia Tian
    • Kai-Jie Wang
    • Chang-Meng Cui
    • Jian-Zhong Cui
  • View Affiliations

  • Published online on: February 19, 2016     https://doi.org/10.3892/ijmm.2016.2495
  • Pages: 921-930
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous research has demonstrated that traumatic brain injury (TBI) activates autophagy and a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In the present study, we investigated the hypothesis that resveratrol (RV), a natural polyphenolic compound with potent multifaceted properties, alleviates brain damage mediated by TLR4 following TBI. Adult male Sprague Dawley rats, subjected to controlled cortical impact (CCI) injury, were intraperitoneally injected with RV (100 mg/kg, daily for 3 days) after the onset of TBI. The results demonstrated that RV significantly reduced brain edema, motor deficit, neuronal loss and improved spatial cognitive function. Double immunolabeling demonstrated that RV decreased microtubule-associated protein 1 light chain 3 (LC3), TLR4‑positive cells co-labeled with the hippocampal neurons, and RV also significantly reduced the number of TLR4‑positive neuron‑specific nuclear protein (NeuN) cells following TBI. Western blot analysis revealed that RV significantly reduced the protein expression of the autophagy marker proteins, LC3II and Beclin1, in the hippocampus compared with that in the TBI group. Furthermore, the levels of TLR4 and its known downstream signaling molecules, nuclear factor-κB (NF-κB), and the inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were also decreased after RV treatment. Our results suggest that RV reduces neuronal autophagy and inflammatory reactions in a rat model of TBI. Thus, we suggest that the neuroprotective effect of RV is associated with the TLR4/NF-κB signaling pathway.
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April-2016
Volume 37 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Feng Y, Cui Y, Gao J, Li M, Li R, Jiang X, Tian Y, Wang K, Cui C, Cui J, Cui J, et al: Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury. Int J Mol Med 37: 921-930, 2016
APA
Feng, Y., Cui, Y., Gao, J., Li, M., Li, R., Jiang, X. ... Cui, J. (2016). Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury. International Journal of Molecular Medicine, 37, 921-930. https://doi.org/10.3892/ijmm.2016.2495
MLA
Feng, Y., Cui, Y., Gao, J., Li, M., Li, R., Jiang, X., Tian, Y., Wang, K., Cui, C., Cui, J."Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury". International Journal of Molecular Medicine 37.4 (2016): 921-930.
Chicago
Feng, Y., Cui, Y., Gao, J., Li, M., Li, R., Jiang, X., Tian, Y., Wang, K., Cui, C., Cui, J."Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury". International Journal of Molecular Medicine 37, no. 4 (2016): 921-930. https://doi.org/10.3892/ijmm.2016.2495