Environmental Enrichment Mitigates Deficits after Repetitive Mild TBI (S9.005)

Objective: To evaluate whether environmental enrichment improves outcomes in an established preclinical repetitive mild traumatic brain injury (rmTBI) model. Background: Environmental enrichment has been shown to improve functional and histologic outcomes in preclinical moderate-severe traumatic brain injury (TBI). However, there is a paucity of preclinical data regarding enrichment strategies in the setting of rmTBI. This is important because enrichment may be a feasible pre and post injury intervention in clinical settings such as collision sports and the military, where the risk of rmTBI is high. Design/Methods: Sixty-nine male C57BL/6 mice were randomized to two different housing conditions, environmental enrichment (EE) or normal condition (NC), then subjected to rmTBI injury (7 injuries in 9 days) or sham injury (anesthesia only). Functional outcomes in three groups (NC-TBI, EE-TBI and NC-sham) were assessed by motor, anxiety/impulsivity and mnemonic behavioral tests. At the synaptic level, NMDAR subunit expression, phosphorylated GluR1, phosphorylated CaMKII and calpain were evaluated by western blot at sub-acute (3 days) and chronic (5 weeks) time points after the last injury. Amyloid precursor protein (APP) was evaluated at chronic time points after injury. Results: Compared to injured NC-TBI mice, EE-TBI mice had improved memory and decreased anxiety and impulsivity after injury, similar to sham performance. Treatment with enrichment also corresponded to normal NMDAR subunit expression, decreased GluR1 phosphorylation, decreased phosphorylated CaMKII and normal calpain expression after rmTBI as well as mitigation of chronic increases in APP after injury. Conclusions: Enrichment strategies may improve functional outcomes and mitigate synaptic changes after rmTBI. As enrichment strategies are feasible in the clinical setting, particularly for athletes and soldiers for whom the risk of repetitive injury is greatest, these data suggest clinical trials may be warranted. Study Supported by: NHL Alumni ProAM tournament Harvard Catalyst T32HD40128-11A1 Disclosure: Dr. Qiu has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Alcon has nothing to disclose. Dr. Hashim has nothing to disclose. Dr. Meehan III has nothing to disclose. Dr. Mannix has nothing to disclose.