L5 Lumbar Laminectomy in Aged C57BL/6J Mice to Model Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) is a common neurological complication following surgery and anesthesia, particularly in older adults, and is associated with delayed recovery, prolonged hospitalization, and reduced quality of life. Orthopedic and spinal procedures are linked to a relatively high risk of POCD; however, preclinical models that closely reflect the perioperative features of spinal surgery remain limited. Commonly used models, including laparotomy and tibial fracture, may produce persistent locomotor impairment and prolonged peripheral inflammation that can confound the interpretation of cognitive behavioral outcomes. Here, this protocol describes a standardized, low-cost protocol for modeling POCD using L5 lumbar laminectomy under sevoflurane anesthesia in 18-month-old male C57BL/6J mice. The procedure is performed using routine surgical instruments and produces a controlled surgical injury while minimizing persistent motor deficits. Cognitive function is evaluated using the novel object recognition test, novel arm Y-maze, and Barnes maze, whereas hippocampal neuronal injury and neuroinflammatory changes are assessed by Nissl staining and Iba1 immunofluorescence, respectively. Representative results demonstrate preserved locomotor activity, impaired cognitive performance, reduced hippocampal neuronal integrity, and enhanced hippocampal neuroinflammation following surgery. This standardized and accessible model provides a clinically relevant platform for investigating the mechanisms underlying spine surgery-associated cognitive dysfunction and for evaluating candidate perioperative neuroprotective interventions.