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

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.

<p>Levonorgestrel Ameliorates Adenomyosis via lncRNA H19/miR-17/TLR4 Pathway</p>

“…Sequence pairing analysis showed that lncRNA H19 and TLR4 shared common binding loci on the miR-17 sequence, and DLR assay confirmed that lncRNA H19 and TLR4 could bind to TLR4 is an important member of cellular immunity and mediates the release of proinflammatory factors, 26 and its abnormal expression may trigger a series of diseases or cancers. [27][28][29][30] In the case of adenomyosis, the inflammatory response induced by TLR4 promotes the excessive proliferation of ESCs and endows them with invasive phenotypes, 31 resulting in the cells to invade to myometrium. According to our findings, LVG reduces the level of TLR4 in ESCs by regulating lncRNA H19/miR-17, thus attenuating the inflammatory response (down-regulation of TNF-α, IL-6, IL-8, IL-17 and IL-1β), and finally suppressing the excessive proliferation and malignant proliferation of ESCs.…”

A Review of Plant Extracts and Plant-Derived Natural Compounds in the Prevention/Treatment of Neonatal Hypoxic-Ischemic Brain Injury

“…Besides, accumulating evidence indicated that RES treatment exerted neuroprotection against various brain disorders [ 247 , 248 , 249 ], including neurodegenerative diseases [ 250 , 251 , 252 ] such as Parkinson’s, Alzheimer’s, and Huntington’s diseases [ 253 , 254 ]. In addition, resveratrol also has neuroprotective effects in animal models of stroke [ 255 ], traumatic brain injury [ 256 ], and various kinds of ischemic brain injury ischemia [ 257 , 258 ] such as focal cerebral ischemia [ 259 , 260 , 261 ], global cerebral ischemia [ 262 , 263 ], and ischemia/reperfusion [ 264 , 265 , 266 , 267 ]. The RES mechanisms of action in neuroprotection might comprise antioxidation [ 268 , 269 ], anti-inflammation [ 270 , 271 ], and anti-apoptosis [ 272 ] effects.…”

Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage

“…A previous study described that resveratrol has reduced infarction volume and brain water content (Dong et al, 2008). This was achieved due to the antioxidative property of resveratrol (Lei, Tu, Wang, Tu, & Shi, 2019). N‐acetyl cysteine (NAC) was also used as a ROS inhibitor for in vitro studies.…”