The involvement of inflammasomes on the learning and memory impairment in a mouse model of embolic stroke

Abstract

Post-stroke cognitive impairment (PSCI) is one of the major complications after a stroke and affects quality of life. Recently, several studies demonstrated that elevated brain proinflammatory cytokines such as TNF-α, IL-6 and IL-1β can induce cognitive impairment. However, the mechanisms underlying PSCI remain unclear. In the present study, we investigated whether post-stroke inflammasomes are involved in the development of PSCI using acetic acid-induced embolic cerebral infarct mice. Long-term learning and memory assessed by the passive avoidance test was impaired on days 7 and 14 after stroke, whereas short-term learning and memory assessed by Y-maze test showed no changes. Also, the expression of the phosphorylated AMPA receptor subunits GluR1 at serine 831 and serine 845 in the dorsal hippocampus were significantly decreased. Under these conditions, inflammasome-related proteins, including caspase-1, ASC/TMS1, IL-1β, TNF-α and IL-18, were significantly increased in the dorsal hippocampus 14 days after stroke. The present findings suggest that a decrease in phosphorylated GluR1 at ser831 and ser845 via the inflammasome activation pathway in the dorsal hippocampus may be involved in the development of learning and memory impairment after embolic stroke.