Animal models of delirium: a narrative review

Delirium is an acute cognitive failure characterized by an acute onset and psychomotor disturbances. It is associated with poor outcomes in hospitalized patients, resulting in prolonged hospital stays, elevated rates of mortality, and cognitive dysfunctions after hospital discharge. The pathophysiology of delirium remains poorly understood, making the development of animal models a promising avenue for researchers to elucidate the mechanisms underlying human delirium. These models not only aid in understanding the pathophysiology and etiology of the disease but also enhance the efficacy of nonpharmacological interventions and identify pharmacological therapies. This review aims to present the most relevant and translational animal models of delirium available in the literature and to provide a critical appraisal of these models using contemporary translational benchmarks. In preclinical models, delirium-like behavior is induced in various methods to reproduce the fundamentals of human delirium, including anesthesia, surgery, sepsis, and drug interventions. However, researchers must select a model encompassing face, construct, predictive, and target validity. Delirium currently lacks pharmacological therapies, and this review is to encourage more researchers to delve deeper and shed light on this medical condition, which is highly prevalent in vulnerable and hospitalized patients.