NLRP6 Inflammasome Ameliorates Brain Injury after Intracerebral Hemorrhage

Wang, Pengfei; Li, Zhenguang; Zhang, Yong; Ju, Xiaohua; Liu, Xinwu; Zhou, Aiming; Chen, Jing

doi:10.3389/fncel.2017.00206

Cited by 20 publications

(15 citation statements)

References 33 publications

(58 reference statements)

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“…Recent studies supposed that the NLRP3 inflammasome in glial cells can detect cellular damage and mediate inflammatory responses during CNS, myocardial, renal, and hepatic I/R injury [16,44]. By contrast, the NLRP6 inflammasome is a critical suppressor of cytokine production [45], which can protect against intracerebral hemorrhage [46] and intestinal inflammation [47]. The expression of inflammasome-associated proteins, such as NLRP3, NLRP6, ASC, and caspase-1, were examined in this study to assess inflammasome activity.…”

Section: Discussionmentioning

confidence: 99%

LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury

Wan¹,

Su²,

Zhang³

et al. 2019

Cell Death Differ

190

159

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Ischemia-reperfusion (I/R) is a common pathology when the blood supply to an organ was disrupted and then restored. During the reperfusion process, inflammation and tissue injury were triggered, which were mediated by immunocytes and cytokines. However, the mechanisms initiating I/R-induced inflammation and driving immunocytes activation remained largely unknown. In this study, we identified long non-coding RNA (lncRNA)-H19 as the key onset of I/R-induced inflammation. We found that I/R increased lncRNA-H19 expression to significantly promote NLRP3/6 inflammasome imbalance and resulted in microglial pyroptosis, cytokines overproduction, and neuronal death. These damages were effectively inhibited by lncRNA-H19 knockout. Specifically, lncRNA-H19 functioned via sponging miR-21 to facilitate PDCD4 expression and formed a competing endogenous RNA network (ceRNET) in ischemic cascade. LncRNA H19/miR-21/PDCD4 ceRNET can directly regulate I/R-induced sterile inflammation and neuronal lesion in vivo. We thus propose that lncRNA-H19 is a previously unknown danger signals in the molecular and immunological pathways of I/R injury, and pharmacological approaches to inhibit H19 seem likely to become treatment modalities for patients in the near future based on these mechanistic findings.

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Section: Discussionmentioning

confidence: 99%

LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury

Wan¹,

Su²,

Zhang³

et al. 2019

Cell Death Differ

190

159

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“…In addition to its role in host defense against bacterial and viral infection-induced inflammation, Nlrp6 has been shown to modulate neuroinflammation. 15,62 In a murine model of acute peripheral nerve injury, Ydens et al 15 Fig. 4 NLRP6 in the gut-liver axis as observed in a study from non-littermate control mice.…”

Section: Nlrp6 In Neuroinflammationmentioning

confidence: 93%

“…In addition to the peripheral nervous system, a role for Nlrp6 in the central nervous system has also been reported. In a murine model of intracerebral hemorrhage (ICH)-induced brain injury, Wang et al 62 analyzed the expression profiles and biological functions of Nlrp6. Nlrp6 expression was increased mainly in glial fibrillary acidic protein-positive astrocytes in the perihematomal brain after ICH downstream of TLR4 activation.…”

Section: Nlrp6 In Neuroinflammationmentioning

confidence: 99%

The NLRP6 inflammasome in health and disease

et al. 2020

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NACHT, LRR (leucine-rich repeat), and PYD (pyrin domain) domain-containing 6 (Nlrp6) is a member of the NLR (nucleotideoligomerization domain-like receptor) family that patrols the cytosolic compartment of cells to detect pathogen-and damageassociated molecular patterns. Because Nlrp6 is a recently discovered inflammasome, details of its signaling mechanism, structural assembly, and roles in host defense have yet to be determined. To date, Nlrp6 has been proposed to perform a multitude of functions ranging from control of microbiota, maintenance of epithelial integrity, and regulation of metabolic diseases to modulation of host defense during microbial infections, cancer protection, and regulation of neuroinflammation. While recent studies have questioned some of the proposed functions of Nlrp6, Nlrp6 has been shown to form an inflammasome complex and cleaves interleukin-1β (IL-1β) and IL-18 during microbial infection, indicating that it is a bonafide inflammasome. In this review, we summarize the recent advancements in knowledge of the signaling mechanisms and structure of the Nlrp6 inflammasome and discuss the relevance of NLRP6 to human disease.

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“…The detailed procedures used to construct the ICH model were established in our previous studies [ 17 ]. Mice were briefly anesthetized intraperitoneally with 4% phenobarbital sodium at a dose of 5 μl/g and were immobilized on the stereotaxic apparatus (RWD Life Science Co, Shenzhen, China).…”

Section: Methodsmentioning

confidence: 99%

“…According to previous methods [ 17 ], for immunohistochemistry staining, the paraffin brain sections were first washed in 0.01 M PBS to remove the cryoprotectant solution. The sections were then incubated overnight at 4°C with the primary antibody goat anti-DCX (1:500, Abcam, UK), rabbit anti-NeuN (1:1000, Abcam, UK), rabbit anti-Sox2 (1:1000, Abcam, UK) and mouse anti-GFAP (1:500, Millipore, Temecula, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Intracerebral hemorrhage influences hippocampal neurogenesis and neurological function recovery via Notch1 signaling

2021

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Intracerebral hemorrhage (ICH) is associated with high rate of mortality and morbidity, but lacks effective therapies. Accumulating studies indicated that the hippocampal neurogenesis plays an essential role in the recovery of neurological function after ICH. The Notch1 signaling pathway shows important roles in neurogenesis. However, the effects of Notch1 on the recovery of neurological function after ICH remain unclear. Here, we used ICH mice model to investigate whether Notch1 signaling was involved in the hippocampal neurogenesis and the recovery of neurological function post-ICH. Our results showed that the rate of symmetric division pattern of hippocampal neural stem cells (NSCs) decreased significantly at 3 days after ICH. Meanwhile, the expression of Notch1 in the hippocampus also was reduced significantly. However, Notch1 activator treatment enhanced the expression of Notch1 and increased the number of Sox2 + GFAP + cells. Further, the rate of symmetric division pattern of NSCs also increased after Notch1 activator treatment in mice with ICH. Importantly, the number of DCX + cells and BrdU + NeuN + in hippocampus were increased on 28 days post-ICH as the Notch1 expression was upregulated. The motor function and spatial memory ability in post-ICH mice following Notch1 activator treatment also were improved. Taken together, our results suggested that Notch1 signaling could influence the recovery of long-term neurological function by regulating the proliferation and differentiation of the hippocampal NSCs in mice after ICH. Our study may provide ideas for the improvement of neurological function and spatial memory defects after ICH.

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NLRP6 Inflammasome Ameliorates Brain Injury after Intracerebral Hemorrhage

Cited by 20 publications

References 33 publications

LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury

LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury

The NLRP6 inflammasome in health and disease

Intracerebral hemorrhage influences hippocampal neurogenesis and neurological function recovery via Notch1 signaling

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