Ischemic stroke leads to neuronal cell death and induces a cascade of inflammatory signals that results in secondary brain damage. Although constant efforts to develop therapeutic strategies and to reveal the molecular mechanism resulting in the physiopathology of this disease, much still remains unclear. Membrane-bound Toll-like receptors (TLRs) and cytosolic nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) are two major families of pattern recognition receptors that initiate pro-inflammatory signaling pathways. In the present study, we explored the role of NLRP10 in regulating inflammatory responses in acute ischemic stroke using the wild type (WT) and NLRP10 knockout (KO) mice by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries. The study first showed that NLRP10 was over-expressed in the ischemic penumbra of WT mice. Then, the brain infarct volume was significantly decreased, and the moving activity was improved post-MCAO in mice with NLRP10 knockout. Apoptosis was also alleviated by NLRP10-knockout, as evidenced by the decreased number of TUNEL-staining cells. Further, NLRP10 deficiency attenuated the activation of glia cells in hippocampus of mice with MCAO operation. NLRP10 inhibition ameliorated the levels of inflammatory factors in peripheral blood serum and hippocampus of mice after stroke. The activation of toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) signaling pathways was markedly suppressed by NLRP10 ablation in mice after MCAO treatment. Importantly, inflammasome, including NLRP12, ASC and Caspase-1, induced by MCAO in hippocampus of mice was clearly impeded by the loss of NLRP10. The results above were mainly verified in LPS-incubated astrocytes in the absence of NLRP10. Correspondingly, in LPS-treated astrocytes, NLRP10 knockout-reduced inflammation via impairing TLR-4/NF-κB and NLRP12/ASC/Caspase-1 pathways was evidently restored by over-expressing NLRP10. Therefore, the results above indicated an essential role of NLRP10 in regulating ischemic stroke, presenting NLRP10 as a promising target to protect human against stroke.

缺血性中风导致神经元细胞死亡，并诱发一系列炎症信号，导致继发性脑损伤。尽管不断努力发展治疗策略并揭示导致该疾病生理病理的分子机制，但仍然有很多不清楚的地方。膜结合的Toll样受体（TLR）和胞质核苷酸结合寡聚域（NOD）样受体（NLR）是模式识别受体的两个主要家族，它们启动了促炎性信号通路。在本研究中，我们探索了NL​​RP10在野生型（WT）和NLRP10基因敲除（KO）小鼠中通过诱导大脑中动脉闭塞/再灌注（MCAO）损伤来调节急性缺血性卒中的炎症反应的作用。该研究首先表明，NLRP10在野生型小鼠的缺血半影中过表达。然后，在具有NLRP10敲除的小鼠中，MCAO后，脑梗塞体积显着减少，并且运动活性得到改善。TURP染色细胞数量的减少证明了NLRP10的敲除也减轻了细胞凋亡。此外，NLRP10缺乏减弱了MCAO手术小鼠海马中神经胶质细胞的激活。NLRP10抑制改善了中风后小鼠外周血血清和海马中炎性因子的水平。MCAO处理后，NLRP10切除可明显抑制Toll样受体（TLR）-4 /核因子-κB（NF-κB）信号通路的激活。重要的是，包括NLRP12，ASC和Caspase-1在内的炎症小体，NLRP10的缺失明显阻止了MCAO在小鼠海马中诱导的凋亡。以上结果主要在没有NLRP10的情况下在LPS孵育的星形胶质细胞中得到验证。相应地，在LPS处理的星形胶质细胞中，过表达NLRP10明显恢复了通过破坏TLR-4 /NF-κB和NLRP12 / ASC / Caspase-1途径而使NLRP10敲除减少的炎症。因此，以上结果表明NLRP10在调节缺血性中风中起着至关重要的作用，这表明NLRP10是保护人类免受中风的有希望的靶标。