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Int. J. Mol. Sci. 2016, 17(8), 1331; doi:10.3390/ijms17081331

Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

1
Department of Neurosurgery, School of Medicine, Nanjing University, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China
2
Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: David Arráez-Román
Received: 5 July 2016 / Revised: 2 August 2016 / Accepted: 8 August 2016 / Published: 12 August 2016
(This article belongs to the Section Bioactives and Nutraceuticals)
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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. View Full-Text
Keywords: toll-like receptor 4; subarachnoid hemorrhage; early brain injury; resveratrol; inflammation toll-like receptor 4; subarachnoid hemorrhage; early brain injury; resveratrol; inflammation
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MDPI and ACS Style

Zhang, X.-S.; Li, W.; Wu, Q.; Wu, L.-Y.; Ye, Z.-N.; Liu, J.-P.; Zhuang, Z.; Zhou, M.-L.; Zhang, X.; Hang, C.-H. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway. Int. J. Mol. Sci. 2016, 17, 1331.

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