Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway
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 und...
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doaj-1868347a59e945eaa3b317063561c0072020-11-25T01:17:21ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-08-01178133110.3390/ijms17081331ijms17081331Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 PathwayXiang-Sheng Zhang0Wei Li1Qi Wu2Ling-Yun Wu3Zhen-Nan Ye4Jing-Peng Liu5Zong Zhuang6Meng-Liang Zhou7Xin Zhang8Chun-Hua Hang9Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaDepartment of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, ChinaToll-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.http://www.mdpi.com/1422-0067/17/8/1331toll-like receptor 4subarachnoid hemorrhageearly brain injuryresveratrolinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiang-Sheng Zhang Wei Li Qi Wu Ling-Yun Wu Zhen-Nan Ye Jing-Peng Liu Zong Zhuang Meng-Liang Zhou Xin Zhang Chun-Hua Hang |
spellingShingle |
Xiang-Sheng Zhang Wei Li Qi Wu Ling-Yun Wu Zhen-Nan Ye Jing-Peng Liu Zong Zhuang Meng-Liang Zhou Xin Zhang Chun-Hua Hang Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway International Journal of Molecular Sciences toll-like receptor 4 subarachnoid hemorrhage early brain injury resveratrol inflammation |
author_facet |
Xiang-Sheng Zhang Wei Li Qi Wu Ling-Yun Wu Zhen-Nan Ye Jing-Peng Liu Zong Zhuang Meng-Liang Zhou Xin Zhang Chun-Hua Hang |
author_sort |
Xiang-Sheng Zhang |
title |
Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway |
title_short |
Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway |
title_full |
Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway |
title_fullStr |
Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway |
title_full_unstemmed |
Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway |
title_sort |
resveratrol attenuates acute inflammatory injury in experimental subarachnoid hemorrhage in rats via inhibition of tlr4 pathway |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-08-01 |
description |
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. |
topic |
toll-like receptor 4 subarachnoid hemorrhage early brain injury resveratrol inflammation |
url |
http://www.mdpi.com/1422-0067/17/8/1331 |
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