Resveratrol downregulates the TLR4 signaling pathway to reduce brain damage in a rat model of focal cerebral ischemia

Lei,Jun‑Rong; Tu,Xian‑Kun; Wang,Yang; Tu,De‑Wen; Shi,Song‑Sheng

doi:10.3892/etm.2019.7324

Resveratrol downregulates the TLR4 signaling pathway to reduce brain damage in a rat model of focal cerebral ischemia

Authors:
- Jun‑Rong Lei
- Xian‑Kun Tu
- Yang Wang
- De‑Wen Tu
- Song‑Sheng Shi
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Affiliations: Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: February 27, 2019 https://doi.org/10.3892/etm.2019.7324
Pages: 3215-3221

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Abstract

Previous studies have demonstrated that inflammation and disruption of the blood‑brain barrier (BBB) are important pathological processes during focal cerebral ischemia. Therefore, the present study evaluated the neuroprotective effects of resveratrol against brain damage, inflammation and BBB disruption in rats with focal cerebral ischemia and assessed the potential underlying molecular mechanisms. Sprague‑Dawley rats underwent cerebral ischemia/reperfusion (IR) and then received intraperitoneal resveratrol (10 and 100 mg/kg) 2 h following the onset of ischemia. Following 24 h of ischemia, neurological deficit scores, cerebral infarctions, morphological characteristics, cerebral water content, myeloperoxidase (MPO) activity and Evans blue extravasation were assessed. Additionally, the protein expression levels of Toll‑like receptor 4 (TLR4) and nuclear factor (NF)‑κB p65 were detected using western blot analyses, the mRNA expression levels of cyclooxygenase‑2 (COX‑2) and matrix metalloproteinase‑9 (MMP‑9) were examined by reverse‑transcription polymerase chain reaction, and tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β blood levels were determined by ELISA. Resveratrol significantly reduced neurological deficit scores, cerebral infarct sizes, neuronal injury, MPO activity and EB content. Cerebral ischemia increased the expression levels of TLR4, NF‑κB p65, COX‑2, MMP‑9, TNF‑α and IL‑1β, but all of these factors were reduced by resveratrol. In conclusion, the present data suggest that resveratrol reduces inflammation, BBB disruption and brain damage in rats following focal cerebral ischemia. Additionally, the neuroprotective effects of resveratrol against cerebral ischemia may be associated with downregulation of the TLR4 pathway.

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