| Traumatic Brain Injury (TBI) refers to injury to brain tissue from external mechanical force, either blunt or penetrating in nature. TBI encompasses both a primary injury (directly resulting from impact) and cascades of secondary injury, in which additional brain tissue is traumatized due to impaired vascular reactivity, excitotoxicity, inflammation, blood brain barrier dysfunction, and ultimate neuronal death. Secondary injury, if untreated, can lead to disability and even death of the individual. Recovery following TBI varies tremendously among individuals. Lifestyle approaches, including diet, mentally-stimulating activities, and social interactions can attenuate cognitive decline associated with normal aging as well as that associated with Alzheimer's disease and other neurodegenerative conditions. Herein, we questioned whether or not such interventions could modulate the extent of secondary injury following experimentally-induced TBI in a mouse model system. To examine this possibility, closed head injury (CHI) was induced in adult C57BI6 mice using a standardized weight drop device. Mice were then maintained under standard diets, enriched (supplemented with omega-3 fatty acids) or deleterious (supplemented with omega-6 fatty acids) diets, in standard or enriched environments (standard mouse cage or enlarged cage with toys), in isolation or in groups. Environmental and social enrichment positively influenced cognitive performance as assayed by maze navigation and Novel Object Recognition (NOR),. Maze navigation was impaired in isolated but not social mice within 1 week and sustained for 4 weeks (the last time tested) post CHI. The impact on isolated mice was exacerbated by the deleterious diet. CHI impaired NOR in all mice but more severely in isolated versus socially-housed mice. Performance of all mice was exacerbated by the deleterious diet. CHI increased corticosterone-induced stress in all mice, which was exacerbated by isolation. CHI increased excitotoxic signaling in hippocampal slices; this was exacerbated in slices from mice maintained in isolation for 2 weeks but not 4 weeks post CHI. Reactive oxygen species and tau phosphorylation were increased in all mice at 2 and 4 weeks post CHI. These findings support the hypothesis that socialization, supplementation with omega-3 fatty acids, and environmental enrichment can attenuate secondary damage and may facilitate recovery following mild TBI. |
