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

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 inves...

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Autores principales: FENG, YAN, CUI, YING, GAO, JUN-LING, LI, MING-HANG, LI, RAN, JIANG, XIAO-HUA, TIAN, YAN-XIA, WANG, KAI-JIE, CUI, CHANG-MENG, CUI, JIAN-ZHONG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790669/
https://www.ncbi.nlm.nih.gov/pubmed/26936125
http://dx.doi.org/10.3892/ijmm.2016.2495
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author FENG, YAN
CUI, YING
GAO, JUN-LING
LI, MING-HANG
LI, RAN
JIANG, XIAO-HUA
TIAN, YAN-XIA
WANG, KAI-JIE
CUI, CHANG-MENG
CUI, JIAN-ZHONG
author_facet FENG, YAN
CUI, YING
GAO, JUN-LING
LI, MING-HANG
LI, RAN
JIANG, XIAO-HUA
TIAN, YAN-XIA
WANG, KAI-JIE
CUI, CHANG-MENG
CUI, JIAN-ZHONG
author_sort FENG, YAN
collection PubMed
description 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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spelling pubmed-47906692016-03-18 Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury FENG, YAN CUI, YING GAO, JUN-LING LI, MING-HANG LI, RAN JIANG, XIAO-HUA TIAN, YAN-XIA WANG, KAI-JIE CUI, CHANG-MENG CUI, JIAN-ZHONG Int J Mol Med Articles 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. D.A. Spandidos 2016-04 2016-02-19 /pmc/articles/PMC4790669/ /pubmed/26936125 http://dx.doi.org/10.3892/ijmm.2016.2495 Text en Copyright: © Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
FENG, YAN
CUI, YING
GAO, JUN-LING
LI, MING-HANG
LI, RAN
JIANG, XIAO-HUA
TIAN, YAN-XIA
WANG, KAI-JIE
CUI, CHANG-MENG
CUI, JIAN-ZHONG
Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title_full Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title_fullStr Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title_full_unstemmed Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title_short Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
title_sort resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the tlr4/nf-κb signaling pathway in experimental traumatic brain injury
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790669/
https://www.ncbi.nlm.nih.gov/pubmed/26936125
http://dx.doi.org/10.3892/ijmm.2016.2495
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