title: Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway.
abstract: Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway.
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. zhangxssp@163.com.
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. lwxzlw@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. njwuqi@gmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. dr.wulingyun@gmail.com.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. ringaly@126.com.
authors.forename: Zhen-Nan
authors.initials: ZN
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. 13677670746@163.com.
authors.forename: Jing-Peng
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. zongzhuang@126.com.
authors.forename: Zong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. mlzhou1979@hotmail.com.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. zhangxssp@gmail.com.|Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. zhangxssp@gmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. hang_neurosurgery@163.com.|Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. hang_neurosurgery@163.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D013267:Stilbenes; D051197:Toll-Like Receptor 4; D000077185:Resveratrol
keywords: early brain injury; inflammation; resveratrol; subarachnoid hemorrhage; toll-like receptor 4