Models of Traumatic Brain Injury in Aged Animals: A Clinical Perspective

Abstract

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States, with advanced age being one of the major predictors of poor prognosis. To replicate the mechanisms and multifaceted complexities of human TBI and develop prospective therapeutic treatments, various TBI animal models have been developed. These models have been essential in furthering our understanding of the pathophysiology and biochemical effects on brain mechanisms following TBI. Despite these advances, translating preclinical results to clinical application, particularly in elderly individuals, continues to be challenging. This review aims to provide a clinical perspective, identifying relevant variables currently not replicated in TBI animal models, to potentially improve translation to clinical practice, especially as it applies to elderly populations. As background for this clinical perspective, we reviewed articles indexed on PubMed from 1970 to 2019 that used aged animal models for studying TBI. These studies examined end points relevant for clinical translation, such as neurocognitive effects, sensorimotor behavior, physiological mechanisms, and efficacy of neuroprotective therapies. However, compared with the higher incidence of TBI in older individuals, animal studies on the basic science of aging and TBI remain remarkably scarce. Moreover, a fundamental disconnect remains between experiments in animal models of TBI and successful translation of findings for treating the older TBI population. In this article, we aim to provide a clinical perspective on the unique attributes of TBI in older individuals and a critical appraisal of the research to date on TBI in aged animal models as well as recommendations for future studies.