Tumor necrosis factor-α inhibitor infliximab alleviates cognitive impairment in mice with transient middle cerebral artery occlusion by decreasing indoleamine 2,3-dioxygenase activity / 国际脑血管病杂志

ABSTRACT

Objective To investigate the role and its mechanism of tumor necrosis factor-α (TNF-α) in post-stroke cognitive impairment (PSCI). Methods Sixty male C57BL/6J mice aged 9-11 weeks were randomly divided into sham operation group, PSCI group, and infliximab group. A PSCI model was induced by middle cerebral artery occlusion. The infliximab group was given infliximab intraperitoneally (10 mg/kg, twice a week), and the PSCI group was injected with an equal volume of normal saline. Water maze and light-dark transition tests were used to evaluate cognitive impairment. Western blot analysis was used to detect hippocampal TNF-α and interleukin-18 ( IL-18 ). The levels of kynurenine and tryptophan in hippocampus were measured by high performance liquid chromatography (HPLC), and the changes of indoleamine 2,3-dioxygenase (IDO) activity (the ratio of kynurenine to tryptophan) were evaluated. Results Morris water maze experiment shows that the escape latency of mice was significantly prolonged in the PSCI group, the target quadrant stay time was significantly shortened, and the number of crossing target quadrants was significantly reduced compared with the sham operation group (all P < 0. 05). The escape latency of the infliximab group was significantly shorter than that of the PSCI group, the target quadrant stay time was significantly prolonged, and the number of crossings increased significantly ( all P < 0. 05 ). Light-dark transition test shows that the latency of the mice was significantly shortened and the number of errors was significantly increased in the PSCI group (all P < 0. 05). The latency of the infliximab group was significantly prolonged compared with the PSCI group, and the number of errors was significantly reduced (all P < 0. 05). Compared with the sham operation group, the levels of TNF-α and IL-18 in the mouse hippocampus of the PSCI group were significantly increased (all P < 0. 05), and the kynurenine/tryptophan ratio was significantly increased (P < 0. 05); the level of TNF-α in hippocampus and the ratio of kynurenine/ tryptophan in the infliximab group were significantly lower than those in the PSCI group (all P < 0. 05). Conclusion TNF-α inhibitor infliximab can alleviate PSCI in mice by reducing IDO activity.