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.

Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease‐specific changes in sleep and incongruous peripheral inflammation

“…Patients with TBI typically experience sleep disturbances both immediately following TBI and months or years after the initial injury (Baumann, 2012; Baumann et al., 2007; Imbach et al., 2016; Sandsmark et al., 2017). Yet, data regarding how TBI affects sleep in the elderly remain sparse, as most research has overwhelmingly focused on young adults and juveniles (Iboaya et al., 2019). A seminal study of elderly patients recently reported that sleep disturbances were more prevalent in older adults that incurred a TBI than in age‐matched adults without a history of TBI (Wei et al., 2020).…”

Experimental model for the study of traumatic brain injury

“…The secondary lesions occur after a period lasting from a few hours to a few days after the primary lesion and they are the result of a tandem of subsequent, metabolic, cellular, and molecular events, which lead in the end to the increase of brain cell death, tissular, vascular and degenerative lesions [ 25 , 26 ].…”

Can Old Animals Reveal New Targets? The Aging and Degenerating Brain as a New Precision Medicine Opportunity for Epilepsy

“…Aging, in general, is associated with cellular, molecular, anatomical, and physiological changes ( 74 ). There are likely also intrinsic processes unique to the aged brain that may promote seizure susceptibility ( 75 ).…”

“…Mitochondrial dysfunction is another pathological feature of both aging and epilepsy ( 78 , 91 ) ( Figure 1 ), which can lead to endogenous production of ROS and apoptosis ( 74 ). Mitochondria fulfill their diverse functions partly through constant remodeling via fission and fusion ( 78 , 91 ).…”