Maresin1 ameliorates postoperative cognitive dysfunction in aged rats by potentially regulating the NF-κB pathway to inhibit astrocyte activation

Abstract

Postoperative cognitive dysfunction (POCD) is one of the most serious postoperative complications in the elderly population. Perioperative central neuroinflammation is considered to be an important pathological mechanism of POCD, with the activation of astrocytes playing a key role in central neuroinflammation. Maresin1 (MaR1) is a specific pro-resolving mediator synthesized by macrophages in the resolution stage of inflammation, and provides unique anti-inflammatory and pro-resolution effects by limiting excessive neuroinflammation and promoting postoperative recovery. However, the question remains whether MaR1 can have a positive effect on POCD. The objective of this study was to investigate the protective effect of MaR1 on POCD cognitive function in aged rats after splenectomy. Morris water maze test and IntelliCage test showed that splenectomy could cause transient cognitive dysfunction in aged rats; however, the cognitive impairment of rats was significantly mitigated when MaR1 pretreatment was administered. MaR1 significantly alleviated the fluorescence intensity and protein expression of glial fibrillary acidic protein and central nervous system specific protein in the cornu ammonis 1 region of the hippocampus. Simultaneously, the morphology of astrocytes was also severely altered. Further experiments showed that MaR1 inhibited the mRNA and protein expression of several key proinflammatory cytokines-interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus of aged rats following splenectomy. The molecular mechanism underlying this process was explored by evaluating expression of components of the nuclear factor κB (NF-κB) signaling pathway. MaR1 substantially inhibited the mRNA and protein expression of NF-κB p65 and κB inhibitor kinase β. Collectively, these results suggest that MaR1 ameliorated splenectomy-induced transient cognitive impairment in elderly rats, and this neuroprotective mechanism may occur through regulating the NF-κB pathway to inhibit astrocyte activation.

Keywords: Aging; Astrocytes; Inflammatory response of central nervous system; Maresin1; NF-κB; Postoperative cognitive dysfunction.