Mice with pre-existing tumors are vulnerable to postoperative cognitive dysfunction

Abstract

Postoperative cognitive dysfunction (POCD) is a common long-term complication of surgery, which may have serious consequences for quality of life and may even result in irreversible cognitive deficits. With the aging of society, more patients are having surgery due to cancer. However, few studies have focused on postoperative cognitive function in cancer patients. Here, MC38 colon cancer cells (2 × 105/mouse) were injected subcutaneously into 2-month-old C57BL/6J mice 3 weeks before surgery to repair tibial fractures in order to establish a model of a tumor-bearing animal undergoing surgery. Both Morris water maze (MWM) and novel object recognition (NOR) tests indicated that cognitive impairment developed after surgery in tumor-bearing mice, whereas a single surgery or tumor alone had no effects on cognitive function in adult mice. The hippocampal expression of postsynaptic density protein 95 (PSD-95) 7 days post-operatively was consistent with the changes seen in the behavioral experiments. At 48 h post-surgery, significantly elevated levels of plasma TNF-α, IL-6 and IL-1β were detected in the tumor-bearing mice, but not in normal mice that had undergone surgery. Further analysis of the hippocampi also showed increased expression of TNF-α, IL-6 and IL-1β in tumor-bearing mice but not normal mice at the same time point, and the mRNA levels of these cytokines were consistent among the different groups. Furthermore, hippocampal microglia activation was absent and the permeability of the BBB was increased in tumor-bearing mice. These results indicate that mice with tumors develop POCD more easily. Prolonged central inflammation, which is mostly likely derived from heightened peripheral innate immunity, possibly underlies the cognitive impairment in tumor-bearing mice after surgery.