Optimization and validation of an animal model for perioperative neurocognitive disorders based on SAMP8 mice.

Abstract

BACKGROUND: Perioperative Neurocognitive Disorders (PND) represent a critical clinical challenge in the elderly. Studies using naturally aged mice are limited by long timelines and high costs. The Senescence-Accelerated Mouse P8 (SAMP8) strain is a promising alternative for modeling age-related conditions. This study aimed to develop a novel PND model using SAMP8 mice to address these limitations. METHODS: Male SAMP8 mice (2∼5 month-old) and 15-month-old C57BL/6 J controls were induced with PND via isoflurane anesthesia and right common carotid artery exposure. Cognitive function was assessed using open field, novel object recognition, and Morris water maze tests. Hippocampal neuroinflammation and synaptic plasticity were analyzed via immunofluorescence, Western blot, and ELISA. The model's responsiveness to intervention was verified using electroacupuncture pretreatment. RESULTS: Post-surgery, 4-month-old SAMP8 mice exhibited cognitive deficits comparable to 15-month-old C57BL/6 J controls, including impaired recognition memory and spatial learning. These were accompanied by significant hippocampal neuroinflammation (microglial activation, elevated IL-6/TNF-α) and reduced synaptic proteins SYN and PSD95. Younger SAMP8 mice (2∼3 month-old) were unaffected. Electroacupuncture pretreatment significantly improved cognitive impairment, confirming the model's responsiveness. CONCLUSION: A highly efficient and cost-effective PND model was successfully established in 4-month-old SAMP8 mice. This model stably recapitulates core PND pathologies and serves as a valuable tool for investigating pathogenesis and screening therapeutic strategies for PND.