Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse

Ye, Xinchun; Shen, Tong; Hu, Jinxia; Zhang, Liang; Zhang, Yunshan; Bao, Lei; Cui, Chengcheng; Jia, Guanghong; Zan, Kun; Zhang, Zuohui; Yang, Xinxin; Shi, Hang; Zu, Jie; Yu, Ming; Song, Chengjie; Wang, Yulan; Qi, Suhua; Cui, Guiyun

doi:10.1016/j.expneurol.2017.03.002

Cited by 110 publications

(69 citation statements)

References 33 publications

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“…In all animals, the adhesive removal and foot-fault tests were performed and the modified neurological severity score (mNSS) was obtained before stroke and at 1, 3, 5, and 7 days after stroke with or without LAM/PIC treatment. The mNSS is a composite that is used to assess neurological functions based on motor, sensory, balance, and reflex measures, which are graded on a scale of 0 to 18 (normal score, 0; maximal deficit score, 18); higher scores imply greater neurological injury [28,29].…”

Section: Neurological Function Testsmentioning

confidence: 99%

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

et al. 2020

J Neuroinflammation

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Background: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Methods: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Results: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. Conclusion: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

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Section: Neurological Function Testsmentioning

confidence: 99%

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

et al. 2020

J Neuroinflammation

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“…Probenecid, a pannexin 1 inhibitor, has also been found to induce astrocyte death and ROS generation, attenuate expression levels of NLRP3 and inhibit the extracellular release of IL-1β (101). Mcc950 and glyburide, both NLRP3 oligomerization inhibitors, reduce infarction volume, neuronal apoptosis, and neurological impairment, and have anti-oxidative stress and anti-inflammatory effects, respectively (102)(103)(104)(105). Recently, several natural compounds, including resveratrol, paeoniflorin and sinomenine, were also demonstrated to reduce cerebral infarction volume, decrease brain water content, improve neurological scores and grip strength, and prevent neuronal cell death following ischemic stroke, through downregulating the expression of the components of the NLRP3 inflammasome and their downstream proteins and attenuating its activation (106)(107)(108).…”

Section: Inhibitors Targeting the Nlrp3 Inflammasome Pathway For Ischmentioning

confidence: 99%

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review)

Liu

Zhang

et al. 2018

Int J Mol Med

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“…Once activated, NLRP3 would oligomerize to form inflammasome and promote maturation of caspase-1 and several proinflammatory cytokines including IL-1β and IL-18 (Shen et al, 2018). Although NLRP3 inflammasome signaling has generally been considered an immune cell-related inflammatory process (Zhou et al, 2016;Lee et al, 2018;Voet et al, 2018;Houtman et al, 2019), expression and activation of inflammasome components have also been reported in neurons (Ye et al, 2017;Teng et al, 2018;Cowie et al, 2019;Pronin et al, 2019); notably, Zhang et al (2016) demonstrated that neuronal activation of NLRP3 is involved in the pathogenesis of PD. However, the potential mechanisms regulating NLRP3 activity in PD are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of HDAC6 Attenuates NLRP3 Inflammatory Response and Protects Dopaminergic Neurons in Experimental Models of Parkinson’s Disease

Yan

Wei

Jian

et al. 2020

Front. Aging Neurosci.

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Aim: To investigate the role of histone deacetylase 6 (HDAC6) deacetylation activity in nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammatory response and explore the effects of pharmacological inhibition of HDAC6 with tubastatin A (TBA) on dopaminergic injury. Methods: Using 6-OHDA-induced Parkinson's disease (PD) models, we examined the effects of TBA on NLRP3 activation and cell injury in SH-SY5Y cells. We also investigated the effects of TBA on NLRP3 inflammatory responses and dopaminergic injury in the nigrostriatal system in mice and analyzed the acetylation levels of peroxiredoxin2 (Prx2) and oxidative stress. Results: TBA inhibited 6-OHDA-induced NLRP3 activation, as demonstrated by decreased expressions of NLRP3 and matured caspase-1 and IL-1β, and also alleviated glial proliferation and dopaminergic neuronal degeneration. Notably, TBA recovered acetylation levels of Prx2 and reduced oxidative stress. Conclusion: Our findings indicate that pharmacological inhibition of HDAC6 with TBA attenuates NLRP3 inflammation and protects dopaminergic neurons, probably through Prx2 acetylation. This study suggests that the deacetylase catalytic domain of HDAC6 is a potential target for PD treatment.

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Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse

Cited by 110 publications

References 33 publications

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review)

Pharmacological Inhibition of HDAC6 Attenuates NLRP3 Inflammatory Response and Protects Dopaminergic Neurons in Experimental Models of Parkinson’s Disease

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