Age-related mechanisms in traumatic brain injury - why are outcomes worse in the elderly?

Abstract

Each year, traumatic brain injury (TBI) claims over 50,000 lives, and leaves 35% of survivors with long term disabilities. Elderly adults often suffer greater morbidity and mortality from TBI. Despite the large and increasing burden of TBI in the elderly, little research has been done to investigate how old age modulates the mechanisms involved in damage and repair after TBI. In previous work, we established a mouse model of sensorimotor TBI, using a controlled cortical impact (CCI) device, magnetic resonance imaging (MRI), and a simple set of behavioral assessments. We now present data regarding age-related questions, using adult male mice (5-6 months old), and aged male mice (22-24 months old). Preliminary data from MRI indicates that while lesion volumes at 14 days post-injury are similar, the extent of edema at 24 hours may be greater in the aged animals (n=4 adult, n=4 aged), suggesting a greater degree of excitoxicity or inflammation. Preliminary data from coronal brain sections stained with the anionic fluorescein Fluoro-Jade B (n=3 adult, n=3 aged), a marker for degenerating neurons, indicate increased damage to hippocampal structures in the aged group, suggesting increased vulnerability of these neurons in the aged brain. Behavioral evaluations (n=8 adult, n=5 aged) show trends towards greater Rotarod deficits in the old animals, and greater deficits in forelimb footfaults in the gridwalk test. Differences in behavioral outcome, MRI and extent of cell death will allow assessment of mechanistic hypotheses.