A modified mouse model of perioperative neurocognitive disorders exacerbated by sleep fragmentation

Abstract

Aging is one of the greatest risk factors for postoperative cognitive dysfunction (POCD), also known as perioperative neurocognitive disorder (PND). Animal models of PND are usually induced in mice over 18 months of age, which imposes expensive economic and time costs for PND-related studies. Sleep disorders, including sleep fragmentation, are reported to aggravate memory impairment in neurocognitive-related diseases such as Alzheimer’s disease (AD). Therefore, the aim of the present study was to explore whether a PND model could be constructed in younger mice with the help of fragmented sleep. We found that fragmented sleep followed by laparotomy under isoflurane anesthesia could stably induce PND in 15-month-old mice. To determine whether the neurocognitive decline in this model could be salvaged by clinical treatments, we administered repetitive transcranial magnetic stimulation (rTMS) to the model mice before anesthesia and surgery. We found that 10 days of high-frequency rTMS (HF-rTMS) could improve spatial learning and memory deficits in this modified PND model. We are the first to successfully construct a PND model in younger mice,which is more economical, that can be used as an alternative model for future PND studies.