A novel rat model of ovarian cancer and cisplatin chemotherapy-related cognitive impairment

Cancer-related cognitive impairment (CRCI) is a common, persistent complication of cancer and its treatment, yet its etiology in ovarian cancer remains poorly understood. Preclinical rat models integrating tumor burden and cognitive outcomes in ovarian cancer remain limited, and the contribution of tumor-associated processes has been insufficiently characterized. We developed an SKOV3.ip1 human ovarian cancer xenograft model of CRCI in female RNU rats, combined with a clinically relevant cisplatin regimen (4 cycles, 5 mg/kg, i.p.). Animals were randomly assigned to non-tumor (NT) or ovarian tumor-bearing (OvT) groups and to receive cisplatin (CDDP) or vehicle (VEH), resulting in four groups: NT + VEH, NT + CDDP, OvT + VEH, and OvT + CDDP. Anxiety-like behavior was assessed using the open field test, and cognitive function was evaluated using context object discrimination and novel object recognition tasks. Serum cytokine levels were measured in relation to behavioral outcomes. CDDP significantly impaired novel object recognition in non-tumor-bearing animals, but not in tumor-bearing animals which were impaired in object recognition regardless of treatment. NT + CDDP, OvT + VEH, and OvT + CDDP animals were significantly impaired relative to NT + VEH. Tumor implantation and cisplatin exposure were associated with alterations in systemic cytokine levels. Exploratory analyses identified IL-10 and C-reactive protein as candidate markers of reduced cognitive performance, although overall discriminative performance was modest. These findings demonstrate that the cognitive effects of chemotherapy depend on tumor status and underscore the importance of incorporating tumor-bearing conditions into preclinical CRCI models. Our model provides a translational platform to investigate tumor-treatment interactions and explore candidate inflammatory markers associated with cognitive outcomes in ovarian cancer.