中风后的后遗症之一——卒中后认知障碍（post-stroke cognitive impairment, PSCI）已被证实与脑前炎症因子如白细胞介素（IL）-1β（IL-1β）和IL-18有关。本研究通过乙酸诱导的栓塞性脑梗死（embolic cerebral infarct, ECI）小鼠模型，探讨了卒中后炎性小体激活在PSCI发展中的作用。行为测试表明，ECI后的长期学习和记忆能力在无动静回避测试中受损，而短期学习和记忆能力在Y迷宫测试中未见明显受损。此外，ECI小鼠背侧海马中磷酸化α-氨基-3-羟基-5-甲基-4-异唑啉丙酸（α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid，AMPA）受体亚单位谷氨酸受体1（glutamate receptor 1, GluR1）的Ser831和Ser845蛋白水平显著降低。此外，ECI小鼠的背侧海马中离子钙结合适配蛋白1（ionized calcium-binding adapter protein 1, Iba1）、胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）、含有半胱氨酸蛋白结合区域的凋亡相关斑点样蛋白-1（apoptosis-associated speck-like protein containing a caspase recruitment domain/target of methylation-induced silencing 1，ASC/TMS1）、Caspase-1、IL-1β、IL-18和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）表达显著增加。这些结果表明，栓塞性脑梗死后发展为PSCI是由于背侧海马中AMPA受体亚单位GluR1在Ser831和Ser845上通过炎性小体激活途径的降低所致。版权所有 © 2023 Elsevier Inc.

Post-stroke cognitive impairment (PSCI) of the complications after stroke has been shown to be involved in brain proinflammatory cytokines such as interleukin (IL)-1β (IL-lβ) and IL-18. In the present study, we examined using acetic acid-induced embolic cerebral infarct (ECI) mice whether post-stroke inflammasome activation is involved in the development of PSCI. In behavioral tests, long-term learning and memory assessed using the passive avoidance test were impaired after ECI. On the other hand, the impairment of short-term learning and memory assessed using the Y-maze test was not observed. Furthermore, the phosphorylated α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) at Ser 831 and Ser 845 protein was found to be significantly decreased in the dorsal hippocampus of ECI mice. In addition, the expression levels of ionized calcium-binding adapter protein 1 (Iba1), glial fibrillary acidic protein (GFAP), apoptosis-associated speck-like protein containing a caspase recruitment domain / target of methylation-induced silencing 1 (ASC/TMS1), Caspase-1, IL-1β, IL-18 and tumor necrosis factor-α (TNF-α) were significantly increased in the dorsal hippocampus of ECI mice. These results indicate that development of PSCI after embolic cerebral infarction is due to a decrease in AMPA receptor subunit GluR1 at Ser831 and Ser845 through the inflammasome activation pathway in the dorsal hippocampus.Copyright © 2023. Published by Elsevier Inc.