Traumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) are two signature illnesses of modern warfare. Discrimination between psychological stress and TBI using a knowledge‐driven unbiased panel of biomarker signatures will be essential for designing precise care management. Recent data suggest a role of alterations of the gut micobiome architecture susceptible to both brain injury and psychological disorders. The present study was conducted to identify factors discriminating between psychological stress and TBI in the fecal microbiome of rats and further to study the effect of diets enriched with varied polyunsaturated fat compositions.A closed‐head TBI model consisting of blast overpressure (BOP) wave exposure coupled with a weight drop concussion (Marmarou method) was used on a group of adult male rats (N=12 each exposed and sham). In parallel, an independent group of rats (N=12 each exposed and sham) was subjected to an underwater trauma (UWT) stressor model that consisted of 30s of swimming and habituation, followed by 30s of forced whole body immersion. Prior to the stress types (BOP or UWT), animals were maintained for six weeks and continued thereafter on two different diets (N=4 per diet group): Standard house chow and custom chow. Unlike the house chow, the custom diets contained no long chain ω‐3 polyunsaturated fatty acids to offset their high Linoleic acid content. The fecal bacterial populations were characterized by identification of 16S ribosomal RNA.Principal coordinate analysis showed clear separation between taxonomic phylogenetic profiles linked to the stress types from their corresponding shams. Within each stress type, the rodents fed on house chow showed different fecal microbial population from the customized diet. Firmicutes, Proteobacteria, and Cyanobacteria were those phyla of interest that showed significant population variance caused by the stress and diet variants. We integrated this microbial profile with rodent blood and brain genomic profile assayed in parallel. The result suggested a significant contribution of gut‐microbiome in energy networks related to the stress response, and diet emerged as a strong candidate in regulating resilience. This outcome could lead in identifying novel customized treatment of TBI and psychological stress.Support or Funding InformationThe project was funded by DoD‐MOMRPThe differential impact of two neurological stress models on different component of gut‐brain axisFigure 1

Blast has been the leading cause of injury, particularly traumatic brain injury and visual system injury, in combat operations in Iraq and Afghanistan. We determined the effect of shock tube-generated primary blast on retinal electrophysiology and on retinal and brain optic tract histopathology in a rat model. The amplitude of a- and b-waves on the electroretinogram (ERG) for both right and left eyes were measured prior to a battlefield simulation Friedlander-type blast wave and on 1, 7, and 14 days thereafter. Histopathologic findings of the right and left retina and the right and left optic tracts (2.8 mm postoptic chiasm) were evaluated 14 days after the blast. For two experiments in which the right eye was oriented to the blast, the amplitude of ERG a- and b-waves at 7 days post blast on the right side but not on the left side was diminished compared to that of sham animals (P = 0.005-0.01) Histopathologic injury scores at 14 days post blast for the right retina but not the left retina were higher than for sham animals (P = 0.01), and histopathologic injury scores at 14 days for both optic tracts were markedly higher than for shams (P < 0.0001). Exposure of one eye to a blast wave, comparable to that causing human injury, produced injury to the retina as determined by ERG and histopathology, and to both postchiasmatic optic tracts as determined by histopathology. This model may be useful for analyzing the effect of therapeutic interventions on retinal damage due to primary blast waves.

Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3), particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET), we measured regional coefficients (K*) and rates (J(in)) of DHA incorporation from plasma into the brain of each group using [1-(11)C]DHA, and regional cerebral blood flow (rCBF) using [(15)O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J(in), the product of K* and unesterified plasma DHA concentration.Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

Docosahexaenoic acid (DHA; 22: 6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-C-11] DHA mostly entered nonbrain organs, with similar to 0.5% entering the brain. Then, using PET and intravenous [1-C-11] DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [O-15] water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate J(in), the product of K*, and the unesterified plasma DHA concentration equaled 3.8 +/- 6 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11C] DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease.-Umhau, J. C., W. Zhou, R. E. Carson, S. I. Rapoport, A. Polozova, J. Demar, N. Hussein, A. K. Bhattacharjee, K. Ma, G. Esposito, S. Majchrzak, P. Herscovitch, W. C. Eckelman, K. A. Kurdziel, and N. Salem, Jr. Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. J. Lipid Res. 2009. 50: 1259-1268.