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.
Keywords: AMPA receptor; Embolic cerebral infarct; Inflammasome; Microglia; Post-stroke cognitive impairment.
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