Behavioral Resiliency of Mice to Repeated Mild Cerebral Concussion: Are there Interactions with Dietary Polyunsaturated Fatty Acids (PUFAs)?

Abstract

Modeling Concussive Brain Injury (CBI) in mice affords opportunities to study mechanisms of neural compromise and therapeutic strategies to promote behavioral recovery. We hypothesized that diets enriched in omega‐3 fatty acids, compared to those with omega‐6 fatty acids, would facilitate both the time and degree of behavioral recovery after mild CBI. This abstract reports the effects, over a 4‐week interval, of 3x‐repeated mild CBI in mice on several behavioral measures across 5 diet groups. Mice were pre‐fed for 5 weeks with 5 different PUFA enriched diets: soy oil; steradonic acid (SDA) enriched ‐ soy oil, corn oil, flaxseed oil and manhedren oil based diets. After week five, CBI was induced in young adult male C57BL6 mice under light isoflurane anesthesia using a cerebral contusion device (impact velocity 3.8 m/sec, dwell .200 sec, deformation 2 mm). Latencies to ‘righting reflex’ after impact clearly showed the CBI animals to be ‘concussed’ compared to shams. However, testing at 2 days post‐CBI and continuing through 4 weeks showed no differences in open field behavior/ambulation, plus‐maze testing, rotarod testing, water‐maze testing, or fear conditioning between any of the groups. This seems similar to psychological stability that is usually seen after mild concussion in humans (i.e., mice subjected to mild CBI also exhibit longer‐term behavioral stability). Thus, the CBI impact parameters used in this study may represent a sub‐threshold effect that do not render permanent CNS disability. More aggressive impact parameters do induce longer lasting CNS deficits in mice. At experiment termination, brains and livers were removed for PUFA analysis by gas chromatography (GC). Analyses did show significant differences between various PUFA concentrations in brain and liver (AA, ALA, LA, SDA, DHA, EPA and DPA) between the different diets, but these were not associated with behavioral resiliency to mild CBI using the parameters mentioned (where no chronic deficits were found). Even so, despite no significant findings with mild CBI, this work provides a baseline to further study mechanisms of neuronal dysfunction and dietary interventions after increasingly severe CBI.Support or Funding InformationSupport: SIU School of Medicine, Neuroscience Research Center, Dept. of Animal Science, Food & Nutrition, SIUC, and Monsanto Co. (St. Louis, MO) who supplied SDA oil.