Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behaviors following exposure to mild TBI (mTBI). Adult, male rats were individually housed in cages fitted with running wheels and daily running distance was recorded throughout the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 days, and 30 days post-injury. Fatty acid composition of food, plasma, and brain tissues was determined. In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 days post-injury. T-tau, GFAP, and UCH-L1 plasma levels did not change at 48 h or 14 days post-injury. However, at 30 days post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). The temporal response of the four injury biomarkers examined is consistent with studies by others demonstrating acute and chronic neural tissue damage following exposure to TBI. The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP, and UCH-L1 following mTBI. Voluntary exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus, the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI.

Approximately 12% of Americans do not consume the recommended level of zinc and could be at risk for marginal zinc deficiency. Zinc functions in antioxidant defense and DNA repair and could be important for prostate health. We hypothesized that marginal zinc deficiency sensitizes the prostate to oxidative stress and DNA damage. Rats were fed a zinc-adequate (ZA; 30 mg Zn/kg) or marginally zinc-deficient (MZD; 5–6 mg Zn/kg) diet for 6 weeks. MZD increased p53 and PARP expression but no change in 8-hydroxy-2′-deoxyguanosine levels was detected. To examine the susceptibility to exogenous oxidative stress, rats fed a ZA or MZD diet were assigned to exercising (EXE) or sedentary (SED) groups for 9 weeks. MZD or EXE alone did not affect oxidative DNA damage in the prostate; however, combined MZD + EXE increased DNA damage in the dorsolateral lobe. PARP and p53 expression was not further induced with MZD + EXE, suggesting that MZD interferes with DNA repair responses to stress. Finally, the addition of phytase to the MZD diet successfully restored zinc levels in the prostate and decreased DNA damage back to ZA levels. Overall, this study suggests that marginal zinc deficiency sensitizes the prostate to oxidative stress and demonstrates the importance of maintaining optimal zinc nutrition in physically active populations.

Objectives Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behavior following exposure to mild TBI (mTBI). Methods Adult, male rats were individually housed in cages fitted with voluntary running wheels and daily running distance was recorded during the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 d and 30 d post-injury. Fatty acid composition of food, plasma and brain tissues was determined. Results In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 d post-injury. T-tau, GFAP and UCH-L1 plasma levels did not change at 48 h or 14 d post-injury. However, at 30 d post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). Conclusions The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP and UCH-L1 following mTBI. Voluntary running exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI. Funding Sources U.S. Army MRDC.

Traumatic brain injury (TBI) results in a complex of physiological and psychological deficits. The study described here utilizes a closed‐head injury Marmarou model. The injuries were caused by the release of a 500 gram steel slug on top of the rat skull between lambda and bregma from a height of 100 cm (to induce mild TBI) or 120 cm (to induce moderate TBI). The focal injury at the point of impact of a steel slug triggers a diffuse secondary‐injury cascade. These focal‐to‐diffuse injuries are known to negatively affect a wide range of cerebral functions that involve multiple brain regions. Here, we sought to contrast the molecular and functional dynamics of two brain regions; one is located at the focal point of injury and other one is located at distal site from the focal injury. The hippocampus is at the focal injury and the cerebellum, although distally removed from the injury site, is within the range of receiving the diffused shock (secondary injury). The Barnes Maze behavioral assays were used to assess the efficacy of processing the retained memories and visuomotor integration in these two regions. The Barnes Maze was performed for five consecutive days starting 14 days post‐injury. A significant delay in latency, defined as learning response to a novel spatial challenge, following mild TBI as compared to pre‐TBI was sustained until the third test day. In moderate TBI, the delay in latency remained significant until the fourth day of maze testing, and the significance declined to a p value = 0.08 on the last day of maze testing.Transcriptomic changes in the hippocampus and cerebellum paralleled the focal‐to‐diffuse responses to TBI. Interestingly, a very different set of genes were significantly perturbed in the hippocampus and cerebellum injured by mild vs. moderate TBI. The underlying differences between the focal‐to‐diffuse TBI responses were further highlighted by downstream functional network analyses. Networks linked to cellular functions remained inhibited, and networks linked to skin cell death remained activated in the hippocampus in moderate TBI 14 days post‐injury.In conclusion, we observed networks that can potentially discriminate mild TBI from moderate TBI and this indicated the role of the hippocampal‐cerebellar interaction in response to TBI. These results reinforce the values of carrying out knowledge‐driven categorization assays to stratify the extent of injuries caused by graded TBI models.Disclaimer: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.Support or Funding InformationFunding support from Military Operational Medicine Research Program, MOMRP is highly acknowledged.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.