Dietary Intake of n-3 Polyunsaturated Fatty Acids Prior to a Mild Traumatic Brain Injury Demonstrates a Dose–Response Effect for Neuroprotective Benefits in Male C57BL/6 Mice

Background: Of the ∼40 million cases of mild traumatic brain injury (mTBI) documented globally each year, the majority are sustained during sports and recreational activities. Evidence has suggested that the use of nutritional supplementation, notably n-3 polyunsaturated fatty acids (PUFA), can provide neuroprotective benefits. Objectives: This study sought to examine the dose-response of consuming an n-3 PUFA diet prior to an mTBI on recovery and functional performance measures in mice. Methods: For 5 wk, male C57BL6/J mice were fed ad libitum on isocaloric diets high in n-3 PUFA (3N3), moderate n-3 PUFA (1N3), or n-6 PUFA (0N3) as a control. At 9-10 wk of age, mice were anesthetized in an induction chamber prior to receiving a mild brain injury induced using a weight-drop injury model. A one-way analysis of variance (ANOVA) with Tukey's post hoc analysis was used to assess between-group differences in functional recovery measures of righting reflex and time to seek) immediately after injury. A repeated measures ANOVA was conducted to determine the effect of diet groups and time on functional performance measures indicated by neurological severity score (NSS) 1, 4, 24, 48, 72, and 168 h (H) post-mTBI. Results: There were no significant differences in recovery measures; however, the 3N3 group demonstrated the fastest recovery post-mTBI and had significantly improved functional performance (P < 0.05) compared with the 0N3 group determined by NSS testing. A one-way ANOVA with Tukey's post hoc indicated that the 3N3 group had significantly improved functional performance (P < 0.05) at 4H post-mTBI compared with the 0N3 group. Conclusions: Overall, these results show that dietary n-3 PUFA confer neuroprotective benefits in mice resulting in significantly improved functional outcomes. This work is relevant to clinical practitioners, athletes, and the general population who aim to support their neurological health through dietary or supplementary n-3 PUFA.