Vitamin D3 Attenuates Delirium-Like Cognitive Impairment in a Postoperative Mouse Model

Biol Pharm Bull. 2026;49(9):1444-1451. doi: 10.1248/bpb.b26-00245.

ABSTRACT

Delirium is an acute neurocognitive impairment triggered by physiological stressors such as medical illness, surgery, or medication use. Although often transient, it is associated with adverse clinical outcomes. Current management primarily relies on nonpharmacological or symptomatic approaches; however, their effectiveness remains limited. Therefore, strategies that target the underlying pathophysiological mechanisms of delirium are of considerable clinical interest. Neuroinflammation has been proposed as a key mechanism in the development of delirium, with inflammatory cytokines produced during systemic inflammation impairing neuronal function. Vitamin D3 (VD3) exerts neuroprotective effects by suppressing the production of inflammatory cytokines. In this study, we hypothesized that VD3 reduces the risk of delirium. To test this hypothesis, a mouse model of postoperative delirium was established using anesthesia and surgery (AS). Cognitive function was assessed using behavioral tests, including the novel object recognition test. Mice subjected to AS exhibited impaired cognitive function, whereas VD3 administration attenuated this impairment. Serum interleukin-6 levels were elevated in the AS group but were reduced following VD3 treatment, consistent with the behavioral findings. These findings suggest that VD3 attenuates cognitive impairment in this postoperative delirium-like mouse model and is associated with reduced serum IL-6 levels. Further studies are required to clarify the underlying mechanisms and the relationship between peripheral and central inflammatory responses.

PMID:42702545 | DOI:10.1248/bpb.b26-00245