Age at Injury as a Modifier of Preclinical TBI Behavioral, Neuropathological, and Inflammatory Outcomes

Abstract

Traumatic brain injury (TBI) is a leading cause of injury-related death and disability. In high-income countries, TBI is most prevalent among the older population (≥65 years), commonly caused by falls. Though age at injury is associated with increased risk of mortality and poor outcome, the underlying mechanisms are unclear. Studies in animal models may yield insights into the intersection of TBI with age. Here we review recent studies in animal models where TBI induced in aged animals is associated with exacerbated behavioral deficits (e.g., mortality, thigmotaxis, and cognitive deficits), neuropathology (microgliosis and astrogliosis), neuroinflammation (e.g., cytokines and iNOS), microglial alterations (e.g., more cellular vesicles and adopting a damage-associated microglia gene signature), and cell signaling and pathway changes (e.g., complement, phagocytosis, autophagy, trophic factor signaling). As relatively few preclinical studies focus on aged animals, more research is needed to fully understand the pathophysiology of TBI in the aged population. Particularly, we recommend that (1) more aged animals should be used, (2) closed-head TBI models should be considered, and (3) animal models of comorbidity or polytrauma should be considered.

Keywords: Age at injury; Age-dependent; Ageing; Behavior; Neuroinflammation; Traumatic brain injury.