Biology subjects

Peskind, E.

Publications and source records attributed to Peskind, E..

3 recordsLinked to original sources

bioRxiv2023

Preliminary cross-sectional investigations into the human glymphatic system using multiple novel non-contrast MRI methods.

We discuss two potential non-invasive MRI methods to cross-sectionally study two distinct facets of the glymphatic system and its association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or cerebrospinal fluid (CSF) movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded multi-delay arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and transendothelial exchange (Tex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N=9, 6F, 23{+/-}3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults, (6F, 67{+/-}3 years old) were imaged after a night of normal sleep only and compared with the young adults. D* in SAS was significantly (p<0.05) lesser after sleep deprivation (0.014{+/-}0.001 mm2/s) than after normal sleep (0.016{+/-}0.001 mm2/s), but was unchanged with aging. Cortical CBF and Tex on the other hand, were unchanged after sleep deprivation but were significantly lower in older adults (37{+/-}3 ml/100g/min, 476{+/-}66 ms) than young adults (42{+/-}2 ml/100g/min, 624{+/-}66 ms). IVIM was thus, sensitive to sleep physiology and multi-echo, multi-delay ASL was sensitive to aging.

neuroscience↗

bioRxiv2022

Timing matters: Sex differences in acute and chronic outcomes following repetitive blast mild traumatic brain injury

BackgroundRepetitive blast-related mild traumatic brain injury (mTBI) caused by exposure to high explosives is increasingly common among warfighters as well as civilians. While women have been serving in military positions with increased risk of blast exposure since 2016, there are few published reports examining sex as a biological variable in models of blast mTBI, greatly limiting diagnosis and treatment capabilities. As such, here we examined acute and chronic outcomes of repetitive blast trauma in female and male mice in relation to potential behavioral, inflammatory, microbiome, and vascular dysfunction. MethodsIn this study we utilized a well-established blast overpressure model to induce repetitive (3x) blast-mTBI in both female and male mice. Acutely following repetitive exposure, we measured serum and brain cytokine levels, blood-brain barrier (BBB) disruption, fecal microbial abundance, and locomotion and anxiety-like behavior in the open field assay. Chronically, in female and male mice we assessed behavioral correlates of mTBI and PTSD-related symptoms commonly reported by Veterans with a history of blast-mTBI using the elevated zero maze, acoustic startle, and conditioned odorant aversion paradigms. ResultsRepetitive blast exposure resulted in both similar and disparate patterns of acute serum and brain cytokine as well as gut microbiome changes in female and male mice. Acute BBB disruption following repetitive blast exposure was apparent in both sexes. While female and male blast mice both exhibited acute locomotor and anxiety-like deficits in the open field assay, only male mice exhibited chronic adverse behavioral outcomes. DiscussionRepresenting a novel survey of potential sex differences following repetitive blast trauma, our results demonstrate unique similar yet divergent patterns of blast-induced dysfunction in female vs. male mice and highlight novel targets for future diagnosis and therapeutic development.

neuroscience↗

bioRxiv2021

An aging clock using metabolomic CSF

Quantifying the physiology of aging is essential for improving our understanding of age-related disease and the heterogeneity of healthy aging. Recent studies have shown that in regression models using "-omic" platforms to predict chronological age, residual variation in predicted age is correlated with health outcomes, and suggest that these "omic clocks" provide measures of biological age. This paper presents predictive models for age using metabolomic profiles of cerebrospinal fluid from healthy human subjects, and finds that metabolite and lipid data are generally able to predict chronological age within 10 years. We use these models to predict the age of a cohort of subjects with Alzheimers and Parkinsons disease and find an increase in prediction error, potentially indicating that the relationship between the metabolome and chronological age differs with these diseases. In our analysis of control subjects, we find the carnitine shuttle, sucrose, biopterin, vitamin E metabolism, tryptophan, and tyrosine to be the most associated with age. We showcase the potential usefulness of age prediction models in a small dataset (n = 85), and discuss techniques for drift correction, missing data imputation, and regularized regression which can be used to help mitigate the statistical challenges that commonly arise in this setting. To our knowledge, this work presents the first multivariate predictive metabolomic and lipidomic models for age using mass spectrometry analysis of cerebrospinal fluid.

systems biology↗