Peroxynitrite activates NLRP3 inflammasome and contributes to hemorrhagic transformation and poor outcome in ischemic stroke with hyperglycemia

Chen, Hansen; Guan, Binghe; Chen, Shuang; Yang, Dan; Shen, Jiangang

doi:10.1016/j.freeradbiomed.2021.01.030

Cited by 20 publications

(17 citation statements)

References 92 publications

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“…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 ). Moreover, glibenclamide is a potent NLRP3 inflammasome inhibitor ( 203 ) that belongs to a class of medications known as sulfonylureas.…”

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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“…Hyperglycemia or diabetics has shown the most eminent effects on stroke so far. Diabetes can amplify NLRP3 and caspase-1 activation in rats after ischemia (Ward et al, 2019), which can mediate the facilitation of tPA-induced BBB damage (Ismael et al, 2020(Ismael et al, , 2021Chen et al, 2021a) and the tendency of HT in ischemic stroke (Ismael et al, 2020). Hyperglycemia induces superimposed effects on caspase-1 in stroke, as specific NLRP3 inhibitor MCC950 showed stronger alleviation of BBB destructions in hyperglycemic stroke than stroke without hyperglycemia (Hong et al, 2018).…”

Section: Other Potential Factors Related To Caspase-1 Activation Processmentioning

confidence: 99%

“…Accumulating evidence have shown caspase-1 activation plays pivotal roles in exacerbating cerebral edema (Wu et al, 2010;Lin et al, 2018;Liang et al, 2019;Li et al, 2020b;Zhang et al, 2020) and increasing the occurrence of HT (Ismael et al, 2018;Chen et al, 2021a) via loosening BBB integrity (Liang et al, 2020). Caspase-1 mainly mediates effects on pyroptosis via pore formation, inflammatory cytokines release and other routes such as apoptosis as well.…”

Section: Caspase-1-dependent Effects On Bbb Dysfunction In Acute Strokementioning

confidence: 99%

“…Caspase-1 has been previously confirmed to mediate BBB disruption in the CNS, specifically critical in ECs' injury and repair of the BBB (Israelov et al, 2020). As specific caspase-1 inhibitors have been confirmed to alleviate BBB deterioration since 2010 (Wu et al, 2010), targeting caspase-1 in stroke contributes to a promising end with a better functional outcome (Wu et al, 2010;Lin et al, 2018;Liang et al, 2019Liang et al, , 2020Li et al, 2020b;Zhang et al, 2020), milder cerebral edema (Wu et al, 2010;Lin et al, 2018;Liang et al, 2019;Li et al, 2020b;Zhang et al, 2020), and lower occurrence of HT (Ismael et al, 2018;Chen et al, 2021a). However, the mechanisms about caspase-1 inhibition on stroke-induced BBB damage remain illdefined yet.…”

Section: Introductionmentioning

confidence: 99%

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Caspase-1: A Promising Target for Preserving Blood–Brain Barrier Integrity in Acute Stroke

Song

Huang

et al. 2022

Front. Mol. Neurosci.

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The blood–brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.

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“… 8 Inflammasome activation was shown to lead to BBB disruption, hemorrhagic transformation, and poor outcomes in hyperglycemic patients suffering from ischemic stroke. 9 Inhibition of caspase‐1, a core inflammasome complex component, might ameliorate ischemia‐associated BBB dysfunction and loss of integrity. 10 Although these findings indicate that inflammasomes are associated with ischemia‐reperfusion injury and BBB damage, the detailed mechanisms remain unknown.…”

Section: Introductionmentioning

confidence: 99%

AIM2 deletion enhances blood‐brain barrier integrity in experimental ischemic stroke

Bian

Shu

et al. 2021

CNS Neurosci Ther

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Peroxynitrite activates NLRP3 inflammasome and contributes to hemorrhagic transformation and poor outcome in ischemic stroke with hyperglycemia

Cited by 20 publications

References 92 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)

Caspase-1: A Promising Target for Preserving Blood–Brain Barrier Integrity in Acute Stroke

AIM2 deletion enhances blood‐brain barrier integrity in experimental ischemic stroke

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