Nervous System Diseases Commons^™

Multi-Site Identification And Generalization Of Clusters Of Walking Behaviors In Individuals With Chronic Stroke And Neurotypical Controls, Natalia Sánchez, Nicolas Schweighofer, Sara J. Mulroy, Ryan T. Roemmich, Trisha M. Keshar, Gelsy Torres-Oviedo, Beth E. Fisher, James M. Finley, Carolee J. Winstein

Physical Therapy Faculty Articles and Research

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Background

Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions.

Objectives

We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: (1) identify clusters of walking behaviors in people post-stroke and neurotypical controls and (2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants.

Methods

We gathered data from 81 post-stroke participants across 4 research sites and …

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Erythrocyte–Brain Endothelial Interactions Induce Microglial Responses And Cerebral Microhemorrhages In Vivo, Hai Zhang, Rachita K. Sumbria, Rudy Chang, Jiahong Sun, David H. Cribbs, Todd C. Holmes, Mark J. Fisher, Xiangmin Xu

Pharmacy Faculty Articles and Research

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Background

Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC–brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.

Methods

RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC–brain endothelial interactions associated with …

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Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

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The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

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Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

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Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Korinne Henslee, Jesse V. Jacobs, Steven C. Cramer

Physical Therapy Faculty Articles and Research

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Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the …

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Mindfulness Meditation As A Complementary Therapy For Chronic Migraines, Isaac Min, Manjari Murali

Student Scholar Symposium Abstracts and Posters

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Migraine headaches, the most common neurological disease across all age groups, affect over one billion individuals worldwide, with symptoms ranging from moderate to severe. Migraines differ in intensity and are accompanied by secondary symptoms, such as neck pain, nausea, and vomiting. Current efforts in treating migraines focus on preventative drug therapy to reduce the frequency of migraine attacks. Although mindfulness-based approaches such as MBSR may serve as an alternative method of reducing the severity of migraine attacks, studies investigating the efficacy of MBSR are limited.

A meta-analysis provides insights into the pathogenesis of migraines through the identification of three genes …

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The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

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Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …

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Brain Volume, Energy Balance, And Cardiovascular Health In Two Nonindustrial South American Populations, Hillard Kaplan, Paul L. Hooper, Margaret Gatz, Wendy J. Mack, E. Meng Law, Helena C. Chui, M. Linda Sutherland, James D. Sutherland, Christopher J. Rowan, L. Samuel Wann, Adel H. Allam, Randall C. Thompson, David E. Michalik, Guido Lombardi, Michael I. Miyamoto, Daniel Eid Rodriguez, Juan Copajira Adrian, Raul Quispe Gutierrez, Bret A. Beheim, Daniel K. Cummings, Edmond Seabright, Sarah Alami, Angela R. Garcia, Kenneth Buetow, Gregory S. Thomas, Caleb E. Finch, Jonathan Stieglitz, Benjamin C. Trumble, Michael D. Gurven, Andrei Irimia

ESI Publications

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Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three …

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Varied Performance Of Picture Description Task As A Screening Tool Across Mci Subtypes, Joan A. Mefford, Zilong Zhao, Leah Heilier, Man Xu, Guifeng Zhou, Rachel Mace, Kelly L. Sloane, Shannon M. Sheppard, Shenly Glenn

Communication Sciences and Disorders Faculty Articles and Research

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A picture description task is a component of Miro Health’s platform for self-administration of neurobehavioral assessments. Picture description has been used as a screening tool for identification of individuals with Alzheimer’s disease and mild cognitive impairment (MCI), but currently requires in-person administration and scoring by someone with access to and familiarity with a scoring rubric. The Miro Health implementation allows broader use of this assessment through self-administration and automated processing, analysis, and scoring to deliver clinically useful quantifications of the users’ speech production, vocal characteristics, and language. Picture description responses were collected from 62 healthy controls (HC), and 33 participants …

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Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

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Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …

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