A Combined Measure of Vascular Risk for White Matter Lesions

This is the author's accepted manuscript.Background Though hypertension is a commonly studied risk factor for white matter lesions (WMLs), measures of blood pressure may fluctuate depending on external conditions resulting in measurement error. Indicators of arterial stiffening and reduced elasticity may be more sensitive indicators of risk for WMLs in aging; however the interdependent nature of vascular indicators creates statistical complications. Objective The purpose of the study was to determine whether a factor score comprised of multiple vascular indicators would be a stronger predictor of WMLs than traditional measures of blood pressure. Methods In a sample of well-characterized nondemented older adults, we used a factor analytic approach to account for variance common across multiple vascular measures while reducing measurement error. The result was a single factor score reflecting arterial stiffness and reduced elasticity. We used this factor score to predict white matter lesion volumes acquired via fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging. Results The combined vascular factor score was a stronger predictor of deep WML (β = 0.42, p < 0.001) and periventricular WML volumes (β = 0.49, p < 0.001). After accounting for the vascular factor, systolic and diastolic blood pressure measurements were not significant predictors. Conclusions This suggests that a combined measure of arterial elasticity and stiffening may be a stronger predictor of WMLs than systolic and diastolic blood pressure accounting for the multicollinearity associated with a variety of interrelated vascular measures

Longitudinal volumetric MRI study of pituitary gland following severe traumatic brain injury

Abstract Purpose: Previous studies have suggested that the hypopituitarism following traumatic brain injury (TBI) is more prevalent than traditionally thought. Conclusion: Following a severe TBI, early pituitary enlargement found in most of our patients persisted in the chronic phases. Our data suggest a potential role of MRI morphometry in early prediction of pituitary dysfunction following head trauma, but further studies including hormonal measurements are necessary for validation

Mitochondrial DNA Manipulations Affect Tau Oligomerization

Background:Mitochondrial dysfunction and tau aggregation occur in Alzheimer’s disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau. Objective:To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations. Methods:Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects. Results:We found cytochrome oxidase activity was particularly sensitive to acute mtDNA depletion, evidence of metabolic re-programming in the ρ0 cells, and a relatively reduced mtDNA content in cybrids generated through AD subject mitochondrial transfer. In each case tau oligomer levels increased, and acutely depleted and AD cybrid cells also showed a monomer to oligomer shift. Conclusion:We conclude a cell’s mtDNA affects tau oligomerization. Overlapping tau changes across three mtDNA-manipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its AD-relevance

Longitudinal volumetric MRI study of pituitary gland following severe traumatic brain injury

Purpose: Previous studies have suggested that the hypopituitarism following traumatic brain injury (TBI) is more prevalent than traditionally thought. The objective of this study was to characterize longitudinal MRI morphometric changes of pituitary gland in patients with severe TBI.Materials and methods: Fourteen patients who had suffered a severe TBI (Glasgow Coma Score=3 - 8) underwent MRI at three time points: Time 1 (mean=31. 5 days), Time 2 (98. 0) and Time 3 (185. 5). The pituitary gland volume was quantified by manually tracing on T1-weighted magnetic resonance images. Data from TBI patients were compared to 14 age- and sex-matched uninjured controls. The relationships between pituitary volumetric measures and patient demographics, length of respiratory support and coma, and presence of intracranial hemorrhage or skull fractures were also analyzed.Results: Following TBI, the pituitary volumes were significantly greater at all three time points: Time 1: median=665mm3, range=460-830mm3, p=0. 007; Time 2: 694mm3, 467-866mm3, 0. 007; and Time 3: 655mm3, 444-795mm3, 0. 015, compared with controls (504mm3, 433-591mm3). At Time 1, pituitary volume was increased in 10 out of 14 patients. Of these, early pituitary enlargements persisted up to six months in nine patients. Pituitary enlargements were negatively correlated with GCS, but not with other variables.Conclusion: Following a severe TBI, early pituitary enlargement found in most of our patients persisted in the chronic phases. Our data suggest a potential role of MRI morphometry in early prediction of pituitary dysfunction following head trauma, but further studies including hormonal measurements are necessary for validation

A Bioenergetics Systems Evaluation of Ketogenic Diet Liver Effects

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author