Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
| Autor: | Yan Feng, Junling Gao, Ran Li, Jianzhong Cui, Ying Cui, Xiaohua Jiang, Ming-Hang Li, Yanxia Tian, Changmeng Cui, Kaijie Wang |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male autophagy Traumatic brain injury Brain damage Pharmacology Motor Activity resveratrol Neuroprotection Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Memory Brain Injuries Traumatic Stilbenes Genetics medicine Animals Neurons biology business.industry traumatic brain injury Autophagy Anti-Inflammatory Agents Non-Steroidal NF-kappa B Brain General Medicine Articles medicine.disease Toll-like receptor 4 030104 developmental biology Neuroprotective Agents nervous system inflammation Immunology TLR4 biology.protein Tumor necrosis factor alpha NeuN medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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