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Main Mechanism of NLRP3 Inflammasome in Development of Atherosclerosis. The phagocytosis of ox-LDL generates ROS through the cathepsin B pathway to activate the NLRP3 inflammasome. Activation of the NLRP3 inflammasome accelerates neutrophil and macrophage recruitment, increases the susceptibility of macrophages to lipid deposition, promotes foam cell formation, induces macrophages secreting IL-1b, and impairs plaque stability. Rupture of atherosclerotic plaques can cause stroke. Ox-LDL also upregulates the expression of the pro-IL-1b. IL-1b inhibits cholesterol efflux through a negative feedback, results in accumulation of intracellular cholesterol and foam cell formation. CD36 converts intracellular soluble ligands into crystals or fibrils, while UDCA increases cholesterol solubility, decreases cholesterol crystals-depositions, and inhibits NLRP3 inflammasome dependent inflammation. HDL play a protective role in atherosclerosis by suppressing monocyte cell recruitment and IL-1b secretion. Abbreviations: ox-LDL: oxidized low-density lipoprotein, ROS: reactive oxygen species, UDCA: ursodeoxycholic acid, HDL: high-density lipoproteins.
Source publication
Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex an...
Contexts in source publication
Context 1
... macrophages are reportedly located in atherosclerotic lesions with NLRP3 inflammasome expression (Paramel Varghese et al., 2016). NLRP3 inflammasome activation accelerates neutrophil and macrophage recruitment and neutrophil extracellular trap formation, increases the susceptibility of macrophages to lipid deposition, and promotes foam cell formation (Figure 2), while Nlrp3 -/-reduces the atherosclerotic lesion size, prevents plaque progression and reduces macrophage infiltration ( Li et al., 2014;Zheng et al., 2014;Leng et al., 2016;Tumurkhuu et al., 2016;Wang et al., 2017;Wang, Wu, et al., 2018;Westerterp et al., 2018;Yan et al., 2018). Furthermore, inhibition of the NLRP3 inflammasome plays an anti-inflammatory role by promoting M1 macrophage transfer into the M2 phenotype ( Abderrazak et al., 2015). ...
Context 2
... downstream factor, IL-1b, of the NLRP3 inflammasome promotes foam cell formation. Ox-LDL upregulates the expression of pro-IL-1b and ROS induced by phagocytosis of ox-LDL through the cathepsin B pathway to activate the NLRP3 inflammasome, induce macrophages to secrete IL-1b, and promote macrophage transfer into foam cells during atherosclerosis ( Figure 2) (Jiang et al., 2012;Ding et al., 2014). IL-1b inhibits cholesterol efflux through negative feedback, resulting in the accumulation of intracellular cholesterol and foam cell formation ( Tumurkhuu et al., 2018). ...
Context 3
... atherosclerotic mice, cholesterol crystals that accumulate in atherosclerotic plaques activate the NLRP3 inflammasome in phagocytes. Thus, decreasing cholesterol crystal deposition in atherosclerotic plaques by employing ursodeoxycholic acid (UDCA) could increase cholesterol solubility in macrophages, impair NLRP3 inflammasomedependent inflammation, and diminish atherosclerotic plaque development ( Figure 2) (Bode et al., 2016). In atherosclerosis, an increase in the pattern recognition receptors CD36 is accompanied by NLRP3 inflammasome activation ( Du et al., 2018). ...
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... water extract of Artemisia scoparia inhibited NFjB and extracellular signal-regulated kinase-mediated expression of NLRP3 and IL-1b precursor genes and proteins ( Ahn et al., 2021). Furthermore, the water extract of Artemisia scoparia participated in the activation response of NLRP3 inflammasome activation, inhibiting cleavage of caspase-1 and IL-1b, and inhibiting ATP-and monosodium uric acid-mediated IL-1b production (Ahn et al., 2021). ...
Context 5
... also inhibited the priming of NLRP3, but not as potently as the interaction of NEK7-NLRP3. Furthermore, Rg3 inhibited both potassium ion effluxindependent activation of the NLRP3 inflammasome and the potassium ion efflux-dependent interaction of NEK7-NLRP3 (Shi et al., 2020). The possibility that Rg3 inhibits potassium ion outflow cannot be excluded, warranting further investigations (Shi et al., 2020). ...
Context 6
... Rg3 inhibited both potassium ion effluxindependent activation of the NLRP3 inflammasome and the potassium ion efflux-dependent interaction of NEK7-NLRP3 (Shi et al., 2020). The possibility that Rg3 inhibits potassium ion outflow cannot be excluded, warranting further investigations (Shi et al., 2020). As NEK7 is a newly discovered component of the NLRP3 inflammasome, limited studies on inhibitors targeting it are available, and exploration of NEK7 inhibitors can be undertaken in the future. ...
Context 7
... NEK7 is a newly discovered component of the NLRP3 inflammasome, limited studies on inhibitors targeting it are available, and exploration of NEK7 inhibitors can be undertaken in the future. Aalinkeel et al. (2018) used nanotechnology to increase the transport of Rg3 on blood-brain barrier, which had a protective effect on Alzheimer's disease (Aalinkeel et al., 2018). The application of nanotechnology to other NLRP3 inflammasome inhibitors is expected to boost the ability of drugs to cross the blood-brain barrier and thus treat neurological diseases. ...
Citations
... A notable feature of pyroptosis is the release of inflammatory factors, including IL-1β and IL-18. The pathways involved in pyroptosis can be categorized into canonical and non-canonical pathways, which are regulated by caspase-1 and caspase-4/5/11, respectively [30,31]. Activation of the caspase-1-mediated canonical pathway leads to upregulated levels of NLRP3 and caspase-1, as well as the release of IL-1β and IL-18 inflammatory bodies [32,33]. ...
Background
Renal fibrosis contributes to chronic renal failure and a decline in the quality of life. Bushen Huoxue (BSHX) formula is a Traditional Chinese Medicine used to treat chronic renal failure. However, its mechanisms of action remain unclear.
Methods and results
In this study, a rat model of renal fibrosis was constructed by 5/6 nephrectomy in vivo, and histopathological changes were analyzed using hematoxylin-eosin and Masson’s trichrome staining. Angiotensin II (Ang II) was used to establish an in vitro renal fibrosis cell model in vitro. Pyroptosis was measured using flow cytometry. Related markers of fibrosis and NOD-like receptor protein 3 (NLRP3) inflammasome activation were measured using western blotting and enzyme-linked immunosorbent assay. Treatment with BSHX (0.25, 0.5, and 1 g/kg) significantly inhibited renal fibrosis and damage in 5/6 nephrectomized rats and simultaneously reduced oxidative stress and NLRP3 inflammasome activation. Similarly, BSHX treatment reduced the levels of hydroxyproline, transforming growth factor-β, matrix metalloproteinase 2, and matrix metalloproteinase 9 and inactivated the Smad2/3 signaling pathway in Ang II-treated HK-2 cells. Our data also showed that treatment with BSHX reduced NLRP3 inflammasome activation and pyroptosis in Ang II-treated HK-2 cells. Moreover, fibrosis and pyroptosis in HK-2 cells induced by NLRP3 overexpression were reduced by treatment with BSHX.
Conclusions
BSHX significantly reduced renal fibrosis and pyroptosis, and its mechanism was mainly associated with the inhibition of reactive oxygen species (ROS)/NLRP3-mediated inflammasome activation.
... Although these studies focused on heat stress-induced apoptosis (another type of cell death) rather than pyroptosis, ROS is known to promote NLRP3 inflammasome activation, GSDMD oligomerization, pore formation, and pyroptosis [116][117][118]. We also now know that tight crossregulation and connection exists between apoptosis, necroptosis, and pyroptosis, indicating the presence of bridges between these pathways to coordinate cell death, in contrast to the previous idea that cell death pathways function in parallel with little or no overlap [119,120]. In a very recent study, by investigating the ROS action on GSDMD, authors found that oxidation of a particular cysteine amino acid in GSDMD protein promotes its oligomerization, pore-forming activity, and ultimately pyroptosis, concluding that this gasdermin family member is a redox-regulated protein which connects cellular redox state to inflammatory cell death [121]. ...
Climate change-induced alterations in temperature variation, ozone exposure, water salinity and acidification, and hypoxia might influence immunity and thus survival in diverse groups of animals from fish to mammals. Pyroptosis is a type of lytic pro-inflammatory programmed cell death, which participates in the innate immune response, and is involved in multiple diseases characterized by inflammation and cell death, mostly studied in human cells. Diverse extrinsic factors can induce pyroptosis, leading to the extracellular release of pro-inflammatory molecules such as IL-18. Climate change-related factors, either directly or indirectly, can also promote animal cell death via different regulated mechanisms, impacting organismal fitness. However, pyroptosis has been relatively less studied in this context compared to another cell death process, apoptosis. This review covers previous research pointing to the potential impact of climate change, through various abiotic stressors, on pyroptotic cell death in different animal cells in various contexts. It was proposed that temperature, ozone exposure, water salinity, water acidification and hypoxia have the potential to induce pyroptotic cell death in animal cells and promote inflammation, and that these pyroptotic events should be better understood to be able to mitigate the adverse effects of climate change on animal physiology and health. This is of high importance considering the increasing frequency, intensity and duration of climate-based changes in these environmental parameters, and the critical function of pyroptosis in immune responses of animals and in their predisposition to multiple diseases including cancer. Furthermore, the need for further mechanistic studies showing the more direct impact of climate change-induced environmental alterations on pyroptotic cell death in animals at the organismal level was highlighted. A complete picture of the association between climate change and pyroptosis in animals will be also highly valuable in terms of ecological and clinical applications, and it requires an interdisciplinary approach.
Significance
Climate change-induced alterations might influence animal physiology. Pyroptosis is a form of cell death with pro-inflammatory characteristics. Previous research suggests that temperature variation, ozone exposure, water salinity and acidification, and hypoxia might have the potential to contribute to pyroptotic cell death in certain cell types and contexts. Climate change-induced pyroptotic cell death should be better understood to be able to mitigate the adverse effects of climate change on animal health.
... The most researched of which are NLRP3 inflammasomes [5,6]. In the host's immunological response to infections and sterile injuries, the NLRP3 inflammasome is essential [7]. One important stage in the activation of inflammasomes is the overexpression of NLRP3 [8]. ...
... Moreover, cytokine levels, including as Tnf, Il6, and Il1b, are downregulated when the NLRP3 inflammasome is inhibited [39]. It is advantageous to inhibit the NLRP3 inflammasome in order to lessen inflammation and the pathological alterations that follow from inflammation [7]. ...
... According to a publication, SIRT1 prevents NLRP3 inflammasome-induced IL-1β production, therefore shielding mesenchymal stem cells from radiation damage [41]. SIRT1 may also deacetylate NF-κB to promote the suppression of NLRP3 inflammasome activation [7]. Inflammation and cell pyroptosis linked to the NLRP3 inflammasome are negatively regulated by SIRT1, and this has an impact on avoiding Ang II-induced HR and malfunction. ...
Background
Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina.
Methods
The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR).
Results
NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models.
Conclusions
SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.
... Extensive evidence suggests that Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3)-mediated inflammasome activation is a vital contributor to diabetesrelated vascular dysfunction and to pro-inflammatory phenotypes [13]. A previous study reported that ROS act as a regulator and trigger of the NLRP3 inflammasome, which then causes Caspase-1-dependent cell pyroptosis [14]. Inflammasomes also play an important role in CKD. ...
Background:
Pyroptosis is a critical form of cell death during the development of chronic kidney disease (CKD). Tripartite motif 6 (TRIM6) is an E3-ubiquitin ligase that participates in the progression renal fibrosis (RF). The aim of this study was to investigate the roles of TRIM6 and Glutathione peroxidase 3 (GPX3) in oxidative stress-induced inflammasome activation and pyroptosis in Ang-II treated renal tubular epithelial cells.
Methods:
To study its role in RF, TRIM6 expression was either reduced or increased in human kidney-2 (HK2) cells using lentivirus, and Ang-II, NAC and BMS-986299 were served as reactive oxygen species (ROS) inducer, ROS scavenger and NLRP3 agonist respectively. Pyroptosis and mitochondrial ROS were measured by flow cytometry. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were determined using commercial kits, while the levels of IL-1β, IL-18, IL-6, and tumor necrosis factor-α (TNF-α) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Co-immunoprecipitation (Co-IP) assay was used to evaluate the interaction between TRIM6 and GPX3. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to measure mRNA and protein expression, respectively.
Results:
Treatment with Angiotensin II (Ang II) increased the protein and mRNA levels of TRIM6 in HK2 cells. Ang II also increased mitochondrial ROS production and the malondialdehyde (MDA) level, but decreased the levels of GSH and SOD. In addition, Ang II enhanced HK2 cell pyroptosis, increased the levels of IL-1β, IL-18, IL-6, and TNF-α, and promoted the expression of active IL-1β, NLRP3, caspase-1, and GSDMD-N proteins. These effects were reversed by knockdown of TRIM6 and by treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. BMS-986299, an NLRP3 agonist treatment, did not affect ROS production in HK2 cells exposed to Ang II combined with NAC, but cell pyroptosis and inflammation were aggravated. Moreover, the overexpression of TRIM6 in HK2 cells resulted in similar effects to Ang II. NAC and GPX3 overexpression in HK2 cells could reverse ROS production, inflammation, and pyroptosis induced by TRIM6 overexpression. TRIM6 overexpression decreased the GPX3 protein level by promoting its ubiquitination, without affecting the GPX3 mRNA level. Thus, TRIM6 facilitates GPX3 ubiquitination, contributing to increased ROS levels and pyroptosis in HK2 cells.
Conclusions:
TRIM6 increases oxidative stress and promotes the pyroptosis of HK2 cells by regulating GPX3 ubiquitination. These findings could contribute to the development of novel drugs for the treatment of RF.
... Currently, NLRP3 inflammasome is considered as a breakthrough to link inflammation and oxidative stress. ROS induces the binding of thioredoxin interacting protein (TXNIP) to NLRP3, leading to NLRP3 inflammasome activation and IL-1β secretion [29]. ROS also activates NLRP3 inflammasome via NF-κB and apoptosis [29]. ...
... ROS induces the binding of thioredoxin interacting protein (TXNIP) to NLRP3, leading to NLRP3 inflammasome activation and IL-1β secretion [29]. ROS also activates NLRP3 inflammasome via NF-κB and apoptosis [29]. Inhibition of the release of inflammatory factors reduces oxidative stress, and inhibition of the downstream pathways of oxidative stress reduces the expression of the NLRP3 inflammasome [30,31]. ...
Oxidative stress is widely involved in the pathological process of ischemic stroke and ischemia-reperfusion. Several research have demonstrated that eliminating or reducing oxidative stress can alleviate the pathological changes of ischemic stroke. However, current clinical antioxidant treatment did not always perform as expected. This bibliometric research aims to identify research trends, topics, hotspots, and evolution on oxidative stress in the field of ischemic stroke, and to find potentially antioxidant strategies in future clinical treatment. Relevant publications were searched from the Web of Science (WOS) Core Collection databases (2001–2022). VOSviewer was used to visualize and analyze the development trends and hotspots. In the field of oxidative stress and ischemic stroke, the number of publications increased significantly from 2001 to 2022. China and the USA were the leading countries for publication output. The most prolific institutions were Stanford University. Journal of Cerebral Blood Flow and Metabolism and Stroke were the most cited journals. The research topics in this field include inflammation with oxidative stress, mitochondrial damage with oxidative stress, oxidative stress in reperfusion injury, oxidative stress in cognitive impairment and basic research and clinical translation of oxidative stress. Moreover, “NLRP3 inflammasome,” “autophagy,” “mitophagy,” “miRNA,” “ferroptosis,” and “signaling pathway” are the emerging research hotspots in recent years. At present, multi-target regulation focusing on multi-mechanism crosstalk has progressed across this period, while challenges come from the transformation of basic research to clinical application. New detection technology and new nanomaterials are expected to integrate oxidative stress into the clinical treatment of ischemic stroke better.
... The NLRP3 inflammasome is one of the most extensively studied inflammasomes in CNS disorders. 28 Activation of the NLRP3 inflammasome in microglia contributes to the development of neuroinflammation and neurodegeneration, while inhibition of the NLRP3 inflammasome reduces the production of proinflammatory cytokines and improves cognitive function. 29 Our previous study also found that NLRP3 activation contributes to CIRI. 15 Upon stimulation, NLRP3 recruits ASC and caspase-1, thereby enabling caspase-1 self-cleavage and activation. ...
Human antigen R (HuR) is a universally expressed RNA‐binding protein that plays an essential role in governing the fate of mRNA transcripts. Accumulating evidence indicated that HuR is involved in the development and functions of several cell types. However, its role in cerebral ischemia/reperfusion injury (CIRI) remains unclear. In this study, we found that HuR was significantly upregulated after CIRI. Moreover, we found that silencing HuR could inhibit the inflammatory response of microglia and reduce the damage to neurons caused by oxygen–glucose deprivation/reperfusion treatment. In vivo, we found that microglial HuR deficiency significantly ameliorated CIRI and reduced NLRP3‐mediated inflammasome activation. Mechanistically, we found that HuR could regulate NLRP3 mRNA stability by binding to the AU‐rich element (ARE) region within the 3′ untranslated region (UTR) of NLRP3 mRNA. In addition, we found that the upregulation of HuR was dependent on the upregulation of NADPH oxidase‐mediated ROS accumulation. Collectively, our studies revealed that HuR could regulate NLRP3 expression and that HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke. Targeting HuR may be a novel therapeutic strategy for cerebral ischemic stroke treatment.
... P2X7R is a ligand-gated cation channel [113], which is activated by extracellular ATP [114]. P2X7R stimulation activates the NLRP3 inflammasome and triggers IL-1β maturation and release [115,116]. ...
Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment.
... Mitochondrial dysfunction, including the overproduction of ROS, uncontrolled mitochondrial autophagy, and abnormal fission and fusion have been implicated in ischemic stroke Lei et al., 2021;Shi et al., 2022b). In addition, apoptosis, ATP disruption, calcium buildup, and faulty mitochondrial biogenesis contribute to aberrant ROS production during ischemic stroke (Bai et al., 2021). ROS release from mitochondria and mitochondrial DNA (mtDNA) damage leads to the activation of the NLRP3 inflammasome and NF-κB pathway . ...
Ischemic-induced neuronal injury arises due to low oxygen/nutrient levels and an inflammatory response that exacerbates neuronal loss. NOD-like receptor family pyrin domain-containing 3 (NLRP3) is an important regulator of inflammation after ischemic stroke, with its inhibition being involved in nerve regeneration. Curcumin, a main active ingredient in Chinese herbs, plays a positive role in neuronal repair and neuroprotection by regulating the NLRP3 signaling pathway. Nevertheless, the signaling mechanisms relating to how curcumin regulates NLRP3 inflammasome in inflammation and neural restoration following ischemic stroke are unknown. In this report, we summarize the main biological functions of the NLRP3 inflammasome along with the neuroprotective effects and underlying mechanisms of curcumin via impairment of the NLRP3 pathway in ischemic brain injury. We also discuss the role of medicinal interventions that target the NLRP3 and potential pathways, as well as possible directions for curcumin therapy to penetrate the blood-brain barrier (BBB) and hinder inflammation in ischemic stroke. This report conclusively demonstrates that curcumin has neuroprotective properties that inhibit inflammation and prevent nerve cell loss, thereby delaying the progression of ischemic brain damage.
... Several cardiovascular diseases, such as hypertension, atherosclerosis, diabetic cardiomyopathy, myocardial infarction, and stroke, are exacerbated by inflammation or oxidative stress (Bai et al., 2021;Tian et al., 2023). Studies on rat models of dexamethasone (DEX) and high-fat-diet-induced programmed hypertension (Hsu et al., 2019;Lin et al., 2018) revealed that 50 mg/kg/day of DMF induced upregulation of Nrf2 mRNA expression, along with a decrease in asymmetric dimethylarginine (ADMA) plasma levels, and the downregulation of the renin-angiotensin system. ...
Dimethyl fumarate (DMF) is an FDA-approved drug for the treatment of psoriasis and multiple sclerosis. DMF is known to stabilize the transcription factor Nrf2, which in turn induces the expression of antioxidant response element genes. It has also been shown that DMF influences autophagy and participates in the transcriptional control of inflammatory factors by inhibiting NF-κB and its downstream targets. DMF is receiving increasing attention for its potential to be repurposed for several diseases. This versatile molecule is indeed able to exert beneficial effects on different medical conditions through a pleiotropic mechanism, in virtue of its antioxidant, immunomodulatory, neuroprotective, anti-inflammatory, and anti-proliferative effects. A growing number of preclinical and clinical studies show that DMF may have important therapeutic implications for chronic diseases, such as cardiovascular and respiratory pathologies, cancer, eye disorders, neurodegenerative conditions, and systemic or organ specific inflammatory and immune-mediated diseases. This comprehensive review summarizes and highlights the plethora of DMF’s beneficial effects and underlines its repurposing opportunities in a variety of clinical conditions.
... Currently, NLRP3 in ammasome is considered as a breakthrough to link in ammation and oxidative stress. ROS induces the binding of thioredoxin interacting protein (TXNIP) to NLRP3, leading to NLRP3 in ammasome activation and IL-1β secretion [27]. ...
... ROS also activates NLRP3 in ammasome via NF-κB and apoptosis [27]. Inhibition of the release of in ammatory factors reduces oxidative stress, and inhibition of the downstream pathways of oxidative stress reduces the expression of the NLRP3 in ammasome [28,29]. ...
Oxidative stress is widely involved in the pathological process of ischemic stroke and ischemia-reperfusion. Several research have demonstrated that eliminating or reducing oxidative stress can alleviate the pathological changes of ischemic stroke. However, current clinical antioxidant treatment did not always perform as expected. This bibliometric research aims to identify research trends, topics, hotspots and evolution on oxidative stress in the field of ischemic stroke, and to find potentially antioxidant strategies in future clinical treatment. Relevant publications were searched from the Web of Science (WOS) Core Collection databases (2001–2022). VOSviewer was used to visualize and analyze the development trends and hotspots. In the field of oxidative stress and ischemic stroke, the number of publications increased significantly from 2001 to 2022. China and the USA were the leading countries for publication output. The most prolific institutions were Stanford University. Journal of Cerebral Blood Flow and Metabolism and Stroke were the most cited journals. The research topics in this field include inflammation with oxidative stress, mitochondrial damage with oxidative stress, oxidative stress in reperfusion injury, oxidative stress in cognitive impairment and basic research and clinical translation of oxidative stress. Moreover, "NLRP3 inflammasome", "autophagy", "mitophagy", "miRNA", "ferroptosis" and "signaling pathway" are the emerging research hotspots in recent years. At present, multi-target regulation focusing on multi-mechanism crosstalk has progressed across this period, while challenges come from the transformation of basic research to clinical application. New detection technology and new nanomaterials are expected to integrate oxidative stress into the clinical treatment of ischemic stroke better.
