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Combat military and civilian law enforcement personnel may be exposed to repetitive low-intensity blast events during training and operations. Persons who use explosives to gain entry (i.e., breach) into buildings are known as “breachers” or dynamic entry personnel. Breachers operate under the guidance of established safety protocols, but despite these precautions, breachers who are exposed to low-level blast throughout their careers frequently report performance deficits and symptoms to healthcare providers. Although little is known about the etiology linking blast exposure to clinical symptoms in humans, animal studies demonstrate network-level changes in brain function, alterations in brain morphology, vascular and inflammatory changes, hearing loss, and even alterations in gene expression after repeated blast exposure. To explore whether similar effects occur in humans, we collected a comprehensive data battery from 20 experienced breachers exposed to blast throughout their careers and 14 military and law enforcement controls. This battery included neuropsychological assessments, blood biomarkers, and magnetic resonance imaging measures, including cortical thickness, diffusion tensor imaging of white matter, functional connectivity, and perfusion. To better understand the relationship between repetitive low-level blast exposure and behavioral and imaging differences in humans, we analyzed the data using similarity-driven multi-view linear reconstruction (SiMLR). SiMLR is specifically designed for multiple modality statistical integration using dimensionality-reduction techniques for studies with high-dimensional, yet sparse, data (i.e., low number of subjects and many data per subject). We identify significant group effects in these data spanning brain structure, function, and blood biomarkers.

Ketogenic diets consist of low carbohydrate/high fat, shifting energy reliance from glucose to ketone bodies. Ketone diester supplement to a standard diet (ketone ester) increases ketone bodies by adding a substance without altering other consumed foods. We evaluated weight, glucose, and ketone concentrations in rats fed ketogenic diet and ketone ester feeds. We hypothesized that these feeds would increase ketones and decrease glucose and weight. We tested 16 male and 16 female Sprague Dawley rats randomly assigned to standard diet, ketogenic diet, or ketone ester for two weeks. Weight and blood glucose and ketones were measured daily. Group means were compared by analysis of variance. Ketogenic diet and ketone ester both increased ketones and decreased weight compared to standard diet (p

Background: Blast exposure is a potential hazard in modern military operations and training, especially for some military occupations. Helmets, peripheral armor, hearing protection, and eye protection worn by military personnel provide some acute protection from blast effects but may not fully protect personnel against cumulative effects of repeated blast overpressure waves experienced over a career. The current study aimed to characterize the long-term outcomes of repeated exposure to primary blast overpressure in experienced career operators with an emphasis on the assessment of hearing and vestibular outcomes.Methods: Participants included experienced “breachers” (military and law enforcement explosives professionals who gain entry into structures through controlled detonation of charges) and similarly aged and experienced “non-breachers” (non-breaching military and law enforcement personnel). Responses to a clinical interview and performance on audiological and vestibular testing were compared.Results: Hearing loss, ringing in the ears, irritability, and sensitivity to light or noise were more common among breachers than non-breachers. Breachers reported more combat exposure than non-breachers, and subsequently, memory loss and difficulty concentrating were associated with both breaching and combat exposure. Vestibular and ocular motor outcomes were not different between breachers and non-breachers.Conclusion: Hearing-related, irritability, and sensitivity outcomes are associated with a career in breaching. Future studies examining long-term effects of blast exposure should take measures to control for combat exposure.

BACKGROUND AND PURPOSE Teriflunomide reduces disability progression and brain atrophy in multiple sclerosis patients. The exact mechanism of action by which teriflunomide exerts these effects is currently unknown. We assessed the effect of teriflunomide on brain glial cells in the Theiler's murine encephalomyelitis virus (TMEV) by using a histological approach in combination with neuroimaging. METHODS Forty-eight SJL female mice received an intracerebral injection of TMEV at 6-8 weeks of age and were then treated with teriflunomide (n = 24) or placebo (n = 24) for 9 months. They were examined with MRI and behavioral testing at 2, 6, and 9 months postinduction (mPI). Of those, 18 teriflunomide-treated and 17 controls mice were analyzed histologically at 9 mPI to sample from different brain regions for myelination status, microglial density, and oligodendroglial lineage. The histological and MRI outcomes were correlated. RESULTS Corpus callosum microglial density was numerically lower in the teriflunomide-treated mice compared to the control group (141.1 ± 21.7 SEM vs. 214.74 ± 34.79 SEM, Iba1+ cells/mm2 , P = .087). Basal ganglia (BG) microglial density in the teriflunomide group exhibited a negative correlation with fractional anisotropy (P = .021) and a positive correlation with mean diffusivity (P = .034), indicating less inflammation and axonal damage. Oligodendroglial lineage cell and myelin density were not significantly different between treatment groups. However, a significant positive correlation between BG oligodendrocytes and BG volume (P = .027), and with N-acetyl aspartate concentration (P = .008), was found in the teriflunomide group, indicating less axonal loss. CONCLUSION Teriflunomide altered microglia density and oligodendrocytes differentiation, which was associated with less evident microstructural damage on MRI.

Theiler’s murine encephalomyelitis virus (TMEV) is a naturally occurring enteric infection, easily passed from mouse to mouse in communal housing. However, TMEV is often inoculated intracerebrally (IC) to produce a mouse model of multiple sclerosis (MS). It has long been accepted that maintaining colonies of IC-infected mice within laboratory animal facilities poses a risk of spreading infection from mouse to mouse via the fecal-oral route as well as contaminated equipment or personnel. Interestingly, the extent of virus shedding from IC-inoculated mice has not been investigated, although several publications have remarked on the lack of virus in the peripheral body of this MS mouse model. Viral shedding, thus infectivity, would require that TMEV escape the central nervous system (CNS) and be found in bodily secretions. We hypothesized that if the virus can escape the CNS, it would be found circulating within blood or other secretions postinjection (PI), after the blood-brain barrier has been experimental...

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls ( P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume ( PConclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

BACKGROUND AND PURPOSE: There is a well-established correlation between deep gray matter atrophy and cognitive dysfunction in MS. However, the cause of these signs of neurodegeneration is poorly understood. Iron accumulation in the deep gray matter is higher in patients with MS compared with age- and sex-matched healthy controls, and could contribute to disease progression. Our objective was to evaluate the relationship between iron and cognition in several deep gray matter structures while accounting for the influence of volume loss. MATERIALS AND METHODS: Eighty-five patients with MS and 27 healthy volunteers underwent 3T MR imaging and neuropsychological examination. We used SWI filtered phase to analyze the mean phase of low-phase voxels, indicative of abnormal iron accumulation. RESULTS: Correlations between mean phase of low-phase voxels and cognitive tests were found in the caudate nucleus (r = 0.240 and 0.232), putamen (r = 0.368, 0.252, and 0.238), globus pallidus (r = 0.235), and pulvinar nucleus of thalamus (r = 0.244, 0.255, and 0.251) (P < .05). However, correlations between structure volume and cognition were more robust. Furthermore, the introduction of structure volume into hierarchical regression analyses after iron metrics significantly improved most models, and mean phase of low-phase voxels did not account for significant variance after volume. CONCLUSIONS: These findings suggest that iron accumulation plays a significant, if minor, role in MS cognitive decline.

Background Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors. Objectives To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler’s Murine Encephalomyelitis Virus, (TMEV) mouse model of MS. Methods Forty-eight (48) mice were infected with TMEV, treated with teriflunomide (24) or control vehicle (24) and followed for 39 weeks. Mice were examined with MRS and volumetric MRI scans (0, 8, 26, and 39 weeks) in the cortex, basal ganglia and thalamus, using a 9.4T scanner, and with behavioral tests (0, 4, 8, 12, 17, 26, and 39 weeks). Within conditions, MRI measures were compared between two time points by paired samples t-test and across multiple time points by repeated measures ANOVA (rmANOVA), and between conditions by independent samples t-test and rmANOVA, respectively. Data were considered as significant at the p