NLRP3 inflammasome activation increases brain oxidative stress after transient global cerebral ischemia in rats

Joaquim, Larissa; Danielski, Lucinéia Gainski; Bonfante, Sandra; Biehl, Erica; Mathias, Khiany; Denicol, Taís; Bagio, Érick; Lanzzarin, Everton; Machado, Richard Simon; Bernades, Gabriela Costa; Generoso, Jaqueline S.; Giustina, Amanda Della; Barichello, Tatiana; Petronilho, Fabrícia

doi:10.1080/00207454.2021.1922402

Cited by 13 publications

(7 citation statements)

References 66 publications

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“…And NLRP3 inflammasome perpetuates oxidative stress. MCC950 application inhibits the effect of NLRP3 on brain oxidative stress in the animal model of transient global cerebral ischemia ( 201 ). In addition, MCC950 administration attenuated brain edema, reduced NADPH oxidase and infarct area and improved the nervous system in a MCAO rat model with reperfusion induced by hyperglycemia ( 202 ).…”

Section: Drugs That Target Mitochondriamentioning

confidence: 99%

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

et al. 2022

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Post-ischemic neuroinflammation induced by the innate local immune response is a major pathophysiological feature of cerebral ischemic stroke, which remains the leading cause of mortality and disability worldwide. NLR family pyrin domain containing (NLRP)3 inflammasome crucially mediates post-ischemic inflammatory responses via its priming, activation and interleukin-1β release during hypoxic-ischemic brain damage. Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. In the present review, focus was addressed on the role of mitochondria in cerebral ischemic stroke while keeping NLRP3 inflammasome as a link. Under ischemia and hypoxia, mitochondria are capable of controlling NLRP3 inflammasome-mediated neuroinflammation through mitochondrial released contents, mitochondrial localization and mitochondrial related proteins. Thus, inflammasome and mitochondria may be attractive targets to treat ischemic stroke as well as the several drugs that target the process of mitochondrial function to treat cerebral ischemic stroke. At present, certain drugs have already been studied in clinical trials.

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Section: Drugs That Target Mitochondriamentioning

confidence: 99%

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

et al. 2022

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“…These results suggested that downregulation of UAF1 might be serve as a NLPR3 inhibitor to assuage SEV-induced neuroinflammation and cognitive impairment. In addition, it has been demonstrated that NLRP3 inhibition could inhibit oxidative stress in brain (Joaquim et al, 2021;Xu et al, 2019). Thus, we conjecture that UFA1 knockdown increased the levels of antioxidative enzymes, likely through downregulating NLRP3 expression.…”

Section: Discussionmentioning

confidence: 73%

Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress

et al. 2022

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Evidence has shown that suppression of the activation of NLRP3 inflammasome could ameliorate surgery/sevoflurane (SEV)-induced post-operative cognitive dysfunction (POCD). However, the underlying mechanisms remain unclear. UAF1 acts as a binding partner of USP1, which inhibits the ubiquitination-mediated degradation of NLRP3, indicating that UAF1 may be implicated in POCD through regulating the NLRP3 inflammasome. Here, we studied the role of UAF1/NLRP3 in SEV-induced cognitive impairment and neurotoxicity in rats. Neonatal rats were randomly divided into control, SEV, SEV+AAV-shNC and SEV+AAV-shUAF1 (UAF1-downregulated) groups. Morris water maze (MWM) test was applied to assess cognitive impairment. TUNEL staining, qRT-PCR and ELISA were used to assess the apoptosis and inflammation markers, respectively. The levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were quantified to determine oxidative stress. The results showed that SEV treatment led to significant cognitive impairment, increased apoptosis in hippocampal tissues, upregulation of MDA and inflammatory factors (TNF-α, IL-1β, IL-18), as well as a decrease in SOD and CAT levels. All of the above observations were reversed by UAF1 downregulation. Furthermore, depletion of UAF1 neutralized SEV-mediated increase in p-NLRP3, p-IκBα and p-p65 levels. Altogether, the current study demonstrated that knockdown of UAF1 could alleviate SEV-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.

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“…After cerebral I/R injury, various cellular responses are aroused, such as the activation of inflammatory cytokines and the accumulation of ROS and other oxygen free radicals (Fann et al, 2013;Guo et al, 2016), which exacerbate I/R injury by promoting brain oxidative stress, inflammation, and cerebral infarction volume (Jiang et al, 2019;Franke et al, 2021;Joaquim et al, 2021). The activation of the NLRP3 inflammasome plays an important role in the development of inflammation after cerebral I/R injury.…”

Section: Inflammationmentioning

confidence: 99%

“…MCC950 can modify the active conformation of NLRP3, and it prevents NLRP3 oligomerization in response to external stimulation (Tapia-Abellán et al, 2019). Experimental studies have found that the treatment of MCC950 could reduce the infarction and edema and improved neurological deficits and BBB integrity via inhibiting inflammatory cytokines, pyroptosis, and brain oxidative stress in the ischemic region after MCAO (Ismael et al, 2018;Bellut et al, 2021;Joaquim et al, 2021). CY-09 could inhibit ATPase activity and block NLRP3 oligomerization to inhibit the activation of NLRP3 inflammasome (Jiang et al, 2017).…”

Section: Novel Inhibitormentioning

confidence: 99%

NLRP3 Inflammasome Activation: A Therapeutic Target for Cerebral Ischemia–Reperfusion Injury

Wang

Ren

et al. 2022

Front. Mol. Neurosci.

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Millions of patients are suffering from ischemic stroke, it is urgent to figure out the pathogenesis of cerebral ischemia–reperfusion (I/R) injury in order to find an effective cure. After I/R injury, pro-inflammatory cytokines especially interleukin-1β (IL-1β) upregulates in ischemic brain cells, such as microglia and neuron. To ameliorate the inflammation after cerebral I/R injury, nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome is well-investigated. NLRP3 inflammasomes are complicated protein complexes that are activated by endogenous and exogenous danger signals to participate in the inflammatory response. The assembly and activation of the NLRP3 inflammasome lead to the caspase-1-dependent release of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18. Furthermore, pyroptosis is a pro-inflammatory cell death that occurs in a dependent manner on NLRP3 inflammasomes after cerebral I/R injury. In this review, we summarized the assembly and activation of NLRP3 inflammasome; moreover, we also concluded the pivotal role of NLRP3 inflammasome and inhibitors, targeting the NLRP3 inflammasome in cerebral I/R injury.

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NLRP3 inflammasome activation increases brain oxidative stress after transient global cerebral ischemia in rats

Cited by 13 publications

References 66 publications

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress

NLRP3 Inflammasome Activation: A Therapeutic Target for Cerebral Ischemia–Reperfusion Injury

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