title: Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury.
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.
authors.affiliation: Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery,Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Gao
authors.affiliation: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Ming-Hang
authors.initials: MH
authors.lastname: Li
authors.affiliation: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Jiang
authors.affiliation: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery,Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China.
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wang
authors.affiliation: Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Chang-Meng
authors.initials: CM
authors.lastname: Cui
authors.affiliation: Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Cui
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013267:Stilbenes; D051197:Toll-Like Receptor 4; D000077185:Resveratrol