Endotoxin tolerance induced by lipopolysaccharide preconditioning protects against surgery‑induced cognitive impairment in aging mice.

Abstract

Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by varying degrees of cognitive functional decline in patients following major surgery. Inflammation and a dysregulated innate immune system exert broad effects in the periphery and central nervous system, yet the mechanisms underlying POCD remain poorly understood and without effective therapy. It has been reported that modulation of the dysregulated inflammatory response with low‑dose lipopolysaccharide (LPS) preconditioning, a phenomenon additionally referred to as endotoxin tolerance, has the potential to reduce neuroinflammation, blood‑brain barrier disruption, and cognitive impairment in a number of disease states. Therefore, it was hypothesized that endotoxin tolerance induced by LPS preconditioning may protect against surgery‑induced cognitive impairment in aging mice. Using a mouse model of surgery‑induced cognitive decline, the present study demonstrated that exploratory laparotomy caused a significant impairment in hippocampal‑dependent memory. Notably, one application of low‑dose LPS preconditioning at 24h prior to surgery improved the cognitive impairment and abolished the signs of neuroinflammation in the hippocampus following surgery. However, LPS injection at 6h or immediately prior to surgery did not confer such beneficial effects, suggesting that the effects of LPS‑induced endotoxin tolerance may depend on the time of application. Inconclusion, the results of the present study suggested that low‑dose LPS preconditioning may markedly alleviate surgery‑induced neuroinflammation and cognitive impairment in aging mice, which may provide a novel approach to preventing POCD and, potentially, other forms of memory impairment.