Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1<i>β</i>Axis in Microglia

Sui, Daming; Xie, Qun; Yi, Wen-Jing; Gupta, Sahil; Yu, Xiuchong; Li, Jinbao; Wang, Jun; Wang, Jiafeng; Deng, Xiaoming

doi:10.1155/2016/1045657

Cited by 105 publications

(85 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we cannot be certain whether the NLRP3 inflammasome contributed to these long-term behavioral alterations. One prior study reported that NLRP3 inflammasome in brain was involved in LPS-induced depressive-like behaviors in mice, and another showed that resveratrol improved the spatial memory of mice with cecal ligation and puncture and inhibited the NLRP3/IL-1β axis in microglia (Zhang et al, 2014; Sui et al, 2016). In our study, we showed that LPS can cause long-term depressive-like behaviors and memory deficit in mice, results that are consistent with those of previous studies (Anderson et al, 2015; Sui et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…One prior study reported that NLRP3 inflammasome in brain was involved in LPS-induced depressive-like behaviors in mice, and another showed that resveratrol improved the spatial memory of mice with cecal ligation and puncture and inhibited the NLRP3/IL-1β axis in microglia (Zhang et al, 2014; Sui et al, 2016). In our study, we showed that LPS can cause long-term depressive-like behaviors and memory deficit in mice, results that are consistent with those of previous studies (Anderson et al, 2015; Sui et al, 2016). Additionally, we found that in brain tissue, the expression of NLRP3 inflammasome and the levels of IL-1β, IL-18, and TNFα were significantly increased in mice on day 3 after LPS injection, indicating that NLRP3 inflammasome was activated.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence indicates that inflammation may play a crucial role in the pathophysiology of anxiety, major depression, and recognition memory deficit (Bayramgurler et al, 2013; Krugel et al, 2013; Comim et al, 2015; Li et al, 2016). Furthermore, several studies have suggested that NLRP3 inflammasome contributes to the development of depressive disorder and memory deficit (Zhang et al, 2014; Alcocer-Gomez et al, 2015; Li et al, 2016; Sui et al, 2016). However, whether NLRP3 inflammasome participates in long-term depressive disorder and recognition memory deficit in mice injected with LPS is not clear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

et al. 2017

View full text Add to dashboard Cite

Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

et al. 2017

View full text Add to dashboard Cite

show abstract

“…38 Similarly, resveratrol treatment decreases the expression of NLRP3 and cleaved IL-1 β in the brain of septic mice. 39 Specifically by using inducible Sirt1 knockout mice, Gao et. al.…”

Section: Discussionmentioning

confidence: 99%

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

Khader

Yang

Hansen

et al. 2017

Journal of Surgical Research

View full text Add to dashboard Cite

Background Sepsis affects 800,000 patients in the US annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis. Materials and Methods Male C57BL/6 mice (20–25g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2 ml saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. Results Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (AST, ALT, and LDH) and renal injury markers (BUN and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines IL-1β and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components [nucleotide oligomerization domain-like receptor protein 3 (NLRP3), adapter apoptosis-associated speck-like protein containing caspase-recruitment domain (ASC), IL-1β, and IL-18] in the liver, compared to the vehicle group. Conclusions SRT1720 treatment attenuates multi-organ injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis.

show abstract

“…Epigenetic modulation (e.g., histone acetylation) participates in the trigger of aberrant glutamate receptor subunits [29,69] and causes memory deficit [70]. In addition, disseminated blood coagulation [71,72] and oxidative stress [73][74][75] aggravated brain dysfunction of SE.…”

Section: Effect Of Cytokine Storm On Brain Functionmentioning

confidence: 99%

In Vivo Imaging of Septic Encephalopathy

Imamura¹,

Murakami²,

Matsumoto³

et al. 2017

Sepsis

View full text Add to dashboard Cite

Septic encephalopathy is a devastating symptom of severe sepsis. Many studies have been performed to uncover the pathophysiological mechanisms of septic encephalopathy; however, novel technical approaches are still required to overcome this complex symptom. Because patients are suffering from severe cognitive impairment, coma, or delirium, which burden not only patients but also caregivers, overcoming septic encephalopathy is still a major social problem worldwide, especially in the intensive care. Septic encephalopathy seems to be caused by cytokine invasion and/or oxidative stress into the brain, and this pathological state leads to imbalance of neurotransmitters. In addition to this pathophysiology, septic encephalopathy causes complicated symptoms (e.g., ischemic stroke, edema, and aberrant sensory function). For these pathophysiological mechanisms, electrophysiology using animal models, positron emission tomography (PET), computed tomography, and magnetic resonance imaging for septic patients has provided important clues. However, the research for septic encephalopathy is currently confronted with the difficulty of complex symptoms. To overcome this situation, in this chapter, we introduce our novel methods for in vivo imaging of septic encephalopathy using near infrared (NIR) nanoparticles, quantum dots. In addition to our recent progress, we propose a strategy for the future approach to in vivo imaging of septic encephalopathy.

show abstract

Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1βAxis in Microglia

Cited by 105 publications

References 36 publications

NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

In Vivo Imaging of Septic Encephalopathy

Contact Info

Product

Resources

About