TABLE 6.

Guidelines and recommendations for preclinical and translational models for delirium

Development of delirium model	Choose species, include both sexes. Choose delirium feature(s) to study, recognizing that high-fidelity models that mimic human delirium are not yet available. Consider face and construct validity in development of model (ie, appropriate age, vulnerability, and precipitating factors [Table 2]) Consider behavioral test(s) and frequency to mimic components of delirium in humans (Table 3). Multiple animal models with different precipitants across different settings maybe required for cross-validation. Carefully control for confounding factors (appetitive, motivational, locomotor, stress-related, illness-induced) that could be inappropriately conflated with delirium-like effects Adhere to current standards for ethical treatment of animals
Experimental framework	Appropriate blinding and randomization of outcome assessments Reproducibility, which requires standardization of protocols and adequate sample sizes Monitoringand physiological control of perturbations, especially anesthesia and infection Standardization of behavioral protocols Consideration of temporal alignment of pathophysiology and behavior
Validation of animal model	Cross-validation of behavioral changes with both human and animal biomarkers (eg, biofluid, EEG, imaging) Testing of animal responses to efficacious pharmacological and nonpharmacological human interventions
Reporting of animal studies	Adherence to PREPARE guidelines119 Standardization and protocol validation Data deposition in publicly accessible databases
Future research priorities	Iterative testing and cross-translation of animal models and human delirium to optimize models, clarify pathophysiological mechanisms, and develop and test therapeutics Large-scale collaborative studies to develop, standardize, and validate animal models for delirium; subsequent alignment with human studies as data become available

Abbreviation: EEG, electroencephalogram; PREPARE, Planning Research and Experimental Procedures on Animals: Recommendations for Excellence