Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, protects against ischemia-induced brain damage in mice by inhibiting inflammatory responses

Li, Ying; Xu, Lanxi; Zeng, Kaiyue; Xu, Zhentian; Suo, Daqin; Lu, Peng; Ren, Tong; Sun, Zhiheng; Yang, Wu; Jin, Xin; Yang, Lichao

doi:10.1016/j.bbi.2017.07.015

Cited by 32 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upregulation of endogenous neuroinflammatory processes is a crucial secondary cell death mechanism that follows ischemic stroke and initiates a feedback loop of inflammatory cascades that can expand the region of brain damage [ 1 ]. Evidence has shown that inflammation not only affects the infarct tissue in the near-term but also causes long-term damage in the ischemic penumbra [ 2 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Ischemic stroke is the most common form of stroke and a major cause of disability and death in adults worldwide. The obstruction of cerebral blood flow initiates the acute phase of cerebral injury, including neuroinflammation and cerebral edema [ 1 ]. Neuroinflammation is a crucial contributor to neuronal death after ischemic stroke, and activated microglia have been the object of studies concentrating on neuroinflammation [ 2 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption

Wang

Zhang

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundAt low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear.MethodsWe investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14.ResultsAmong mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1β. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-β, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9.ConclusionCORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption

Wang

Zhang

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…In order to further confirm the effect of kellerin on regulating microglial phenotype, in vitro experiments were also carried out. The inflammatory events in ischemic brain can be simulated in vitro by exposing BV‐2 cells to cytokines (Li et al, ; Wang et al, ; Yang et al, ; Yuan et al, ). BV‐2 cells stimulated with LPS are the most popular model to mimic the microglial M1 phenotype that is induced in ischemic stroke (Han et al, ; Liu et al, ; Xiang, Xiao, Shen, & Li, ).…”

Section: Discussionmentioning

confidence: 99%

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Zhang

Jiang

et al. 2020

Phytotherapy Research

View full text Add to dashboard Cite

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.

show abstract

“…And their data provided the evidence of pioglitazone for secondary prevention of ischemic stroke in Asian T2DM patients, which provides a theoretical basis for the development of new cardiovascular and cerebrovascular disease drugs (9). The research progress of PPARγ agonists in the treatment of CI/RI in the last 5 years is summarized in the Table 1 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Peroxisome Proliferator-Activated Receptor Gamma in Cerebral Ischemia-Reperfusion Injury

et al. 2020

View full text Add to dashboard Cite

Cerebral ischemia-reperfusion injury (CI/RI) is a complex pathological process that often occurs secondary to trauma, surgery, and shock. Peroxisome proliferator activated receptor gamma (PPARγ) is a subunit of the PPAR and is a ligand-activated nuclear transcription factor. After being activated by its ligand, PPARγ can combine with specific DNA response elements to regulate the transcription and expression of genes. It has a wide range of biological functions, such as regulating lipid metabolism, improving insulin sensitivity, modulating anti-tumor mechanisms, and inhibiting inflammation. In recent years, some studies have shown that PPARγ exerts a protective effect during CI/RI. This article aims to summarize the research progress of studies that have investigated the protective effects of PPARγ in CI/RI and the cellular and molecular mechanisms through which these effects are modulated, including inhibition of excitatory amino acid toxicity, reduced Ca 2+ overload, anti-oxidative stress, anti-inflammation, inhibition of microglial activation, maintain the BBB, promotion of angiogenesis, and neurogenesis and anti-apoptotic processes.

show abstract

Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, protects against ischemia-induced brain damage in mice by inhibiting inflammatory responses

Cited by 32 publications

References 41 publications

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

The Protective Effects of Peroxisome Proliferator-Activated Receptor Gamma in Cerebral Ischemia-Reperfusion Injury

Contact Info

Product

Resources

About