Nervous System Diseases Commons^™

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …

Functional Seizures: The Patient’S Perspective Of A Diagnostic And Treatment Odyssey, Heather J. Andrini, Sydni L. Au Hoy, Ashley M. Okhovat, Juliana Lockman, Gregory R. Goldsmith

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Functional seizures can be challenging to properly diagnose, often leading to delays in treatment. The etiology of functional seizures is multifactorial, with psychological factors identified in many, but not all cases. Misdiagnosis may occur due to clinical features mimicking other medical conditions. Once a correct diagnosis is reached, delivery of definitive, evidence-based treatment may be challenging due to limited availability of specialized resources. Research shows psychological education and cognitive behavioral therapy (CBT) have the greatest efficacy. However, individual differences, including acceptance of the diagnosis, therapeutic alliance, duration of symptoms, comorbidities, and access to care may influence outcomes. There is a …

The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Accurately measuring the brain concentration of a neurotherapeutic is critical in determining its pharmacokinetic profile in vivo. Biologics are potential therapeutics for neurologic diseases and biologics fused to an antibody targeting a transcytosis receptor at the Blood-Brain Barrier, designated as antibody-biologic fusion proteins, are Blood-Brain Barrier penetrating neurotherapeutics. The use of sandwich immunosorbent assays to measure concentrations of antibody-biologic fusion proteins in brain homogenates has become increasingly popular. The raw brain homogenate contains many proteins and other macromolecules that can cause a matrix effect, potentially interfering with the limit of detection of such assays and reduce the overall sample …

Kinematic Assessment Of Turning And Walking Tasks Among Stroke Survivors By Employing Wearable Sensors And Pressure Platform, Masoud Abdollahi, Pranav Madhav Kuber, Christopher Hoang, Michael Shiraishi, Rahul Soangra, Ehsan Rashedi

Physical Therapy Faculty Articles and Research

Stroke survivors often experience reduced movement capabilities due to alterations in their neuromusculoskeletal systems. Modern sensor technologies and motion analyses can facilitate the determination of these changes. Our work aims to assess the potential of using wearable motion sensors to analyze the movement of stroke survivors and identifying the affected functions. We recruited 10 participants (5 stroke survivors, 5 healthy individuals) and conducted a controlled laboratory evaluation for two of the most common daily activities: turning and walking. Among the extracted kinematic parameters, range of trunk and sacrum lateral bending in turning were significantly larger in stroke survivors (p-value<0.02). However, no statistical difference in mean angular velocity and range of motion for trunk/sacrum/shank flexion-extension were obtained in the turning task. Our results also indicated that during walking, while there was no difference in swing time, double support portion of gait among the stroke group was significantly larger (p-value = 0.001). Outcomes of this investigation may help in designing new rehabilitation programs for stroke and other neurological disorders and/or in improving the efficacy of such programs.Clinical Relevance— This study may provide a better insight on the detailed functional differences between stroke survivors and healthy individuals which in turn could be used to develop a more efficient rehabilitation program for stroke community.

Self-Paced Treadmills Do Not Allow For Valid Observation Of Linear And Nonlinear Gait Variability Outcomes In Patients With Parkinson’S Disease, Maryam Rohafza, Rahul Soangra, Jo Armour Smith, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Background

Due to the imposed constant belt speed, motorized treadmills are known to affect linear and nonlinear gait variability outcomes. This is particularly true of patients with Parkinson’s Disease where the treadmill can act as an external pacemaker. Self-paced treadmills update the belt speed in response to the subject's walking speed and might, therefore, be a useful tool for measurement of gait variability in this patient population. This study aimed to compare gait variability during walking at self-paced and constant treadmill speeds with overground walking in individuals with PD and individuals with unimpaired gait.

Methods

Thirteen patients with Parkinson’s Disease …

Dysfunctional Tissue Correlates Of Unrelated Naming Errors In Acute Left Hemisphere Stroke, Erin L. Meier, Shannon M. Sheppard, Emily B. Goldberg, Catherine R. Kelly, Alexandra Walker, Delaney M. Ubellacker, Emilia Vitti, Kristina Ruch, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalised with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within …

Does Subthalamic Deep Brain Stimulation Impact Asymmetry And Dyscoordination Of Gait In Parkinson’S Disease?, Deepak K. Ravi, Christian R. Baumann, Elena Bernasconi, Michelle Gwerder, Niklas K. Ignasiak, Mechtild Uhl, Lennart Stieglitz, William R. Taylor, Navrag B. Singh

Physical Therapy Faculty Articles and Research

Background. Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for selected Parkinson’s disease (PD) patients. Gait characteristics are often altered after surgery, but quantitative therapeutic effects are poorly described. Objective. The goal of this study was to systematically investigate modifications in asymmetry and dyscoordination of gait 6 months postoperatively in patients with PD and compare the outcomes with preoperative baseline and to asymptomatic controls without PD. Methods. A convenience sample of thirty-two patients with PD (19 with postural instability and gait disorder (PIGD) type and 13 with tremor dominant disease) and 51 asymptomatic controls participated. Parkinson patients …

Scoping Review: The Empowerment Of Alzheimer’S Disease Caregivers With Mhealth Applications, Eunhee Kim, Andrius Baskys, Anandi V. Law, Moom R. Roosan, Yan Li, Don Roosan

Pharmacy Faculty Articles and Research

Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative chronic diseases. As it progresses, patients become increasingly dependent, and their caregivers are burdened with the increasing demand for managing their care. Mobile health (mHealth) technology, such as smartphone applications, can support the need of these caregivers. This paper examines the published academic literature of mHealth applications that support the caregivers of AD patients. Following the PRISMA for scoping reviews, we searched published literature in five electronic databases between January 2014 and January 2021. Twelve articles were included in the final review. Six themes emerged based on the functionalities provided …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Lesion Loci Of Impaired Affective Prosody: A Systematic Review Of Evidence From Stroke, Alexandra Zezinka Durfee, Shannon M. Sheppard, Margaret L. Blake, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Affective prosody, or the changes in rate, rhythm, pitch, and loudness that convey emotion, has long been implicated as a function of the right hemisphere (RH), yet there is a dearth of literature identifying the specific neural regions associated with its processing. The current systematic review aimed to evaluate the evidence on affective prosody localization in the RH. One hundred and ninety articles from 1970 to February 2020 investigating affective prosody comprehension and production in patients with focal brain damage were identified via database searches. Eleven articles met inclusion criteria, passed quality reviews, and were analyzed for affective prosody localization. …

Neural Regions Underlying Object And Action Naming: Complementary Evidence From Acute Stroke And Primary Progressive Aphasia, Bonnie L. Breining, Andreia V. Feria, Brian Caffo, Erin L. Meier, Shannon M. Sheppard, Rajani Sebastian, Donna C. Tippett, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Background: Naming impairment is commonly noted in individuals with aphasia. However, object naming receives more attention than action naming. Furthermore, most studies include participants with aphasia due to only one aetiology, commonly stroke. We developed a new assessment, the Hopkins Action Naming Assessment (HANA), to evaluate action naming impairments.

Methods >& Procedures: Participants (N = 138 PPA, N = 37 acute stroke) completed the BNT and HANA. Behavioural performance was compared. A subset of participants (N = 31 PPA, N = 37 acute stroke) provided neuroimaging data. The whole brain was automatically segmented into regions of interest (ROIs). …

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K^{+ …}

Characterizing Subtypes And Neural Correlates Of Receptive Aprosodia In Acute Right Hemisphere Stroke, Shannon M. Sheppard, Erin L. Meier, Alexandra Zezinka Durfee, Alex Walker, Jennifer Shea, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Introduction: Speakers naturally produce prosodic variations depending on their emotional state. Receptive prosody has several processing stages. We aimed to conduct lesion-symptom mapping to determine whether damage (core infarct or hypoperfusion) to specific brain areas was associated with receptive aprosodia or with impairment at different processing stages in individuals with acute right hemisphere stroke. We also aimed to determine whether different subtypes of receptive aprosodia exist that are characterized by distinctive behavioral performance patterns.

Methods: Twenty patients with receptive aprosodia following right hemisphere ischemic stroke were enrolled within five days of stroke; clinical imaging was acquired. Participants completed …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …