Medical Sciences Commons^™

Dementia Risk Reduction: Why Haven't The Pharmacological Risk Reduction Trials Worked? An In-Depth Exploration Of Seven Established Risk Factors, Ruth Peters, John Breitner, Sarah James, Gregory A. Jicha, Pierre-Francois Meyer, Marcus Richards, A. David Smith, Hussein N. Yassine, Erin L. Abner, Atticus H. Hainsworth, Patrick G. Kehoe, Nigel Beckett, Christopher Weber, Craig Anderson, Kaarin J. Anstey, Hiroko H. Dodge

Neurology Faculty Publications

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need …

Multi-Vendor And Multisite Evaluation Of Cerebrovascular Reactivity Mapping Using Hypercapnia Challenge, Peiying Liu, Dengrong Jiang, Marilyn Albert, Christopher E. Bauer, Arvind Caprihan, Brian T. Gold, Steven M. Greenberg, Karl G. Helmer, Kay Jann, Gregory A. Jicha, Pavel Rodriguez, Claudia L Satizabal, Sudha Seshadri, Herpreet Singh, Jeffrey F. Thompson, Danny J. J. Wang, Hanzhang Lu

Neuroscience Faculty Publications

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate …

Stimulating The Facial Nerve To Treat Ischemic Stroke: A Systematic Review, Turner S. Baker, Justin Robeny, Danna Cruz, Alexis Bruhat, Alfred-Marc Iloreta, Anthony Costa, Thomas James Oxley

Publications and Research

Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation …

Cessation And Resumption Of Elective Neurointerventional Procedures During The Coronavirus Disease 2019 Pandemic And Future Pandemics, Tim W. Malisch, Sameer A. Ansari, Gary R. Duckwiler, Kyle M. Fargen, Steven W. Hetts, Franklin A. Marden, Athos Patsalides, Clemens M. Schirmer, Allan Brook, Justin F. Fraser

Neurosurgery Faculty Publications

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on …

Mitochondrial Phenotypes In Purified Human Immune Cell Subtypes And Cell Mixtures, Shannon Rausser, Caroline Trumpff, Marlon A. Mcgill, Alex Junker, Wei Wang, Siu-Hong Ho, Anika Mitchell, Kalpita R. Karan, Catherine Monk, Suzanne C. Segerstrom, Rebecca G. Reed, Martin Picard

Psychology Faculty Publications

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning four decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, …

Longitudinal Cognitive Performance Of Alzheimer's Disease Neuropathological Subtypes, Madeline Uretsky, Laura E. Gibbons, Shubhabrata Mukherjee, Emily H. Trittschuh, David W. Fardo, Patricia A. Boyle, C. Dirk Keene, Andrew J. Saykin, Paul K. Crane, Julie A. Schneider, Jesse Mez

Sanders-Brown Center on Aging Faculty Publications

Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments.

Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive …

Leveraging High-Resolution 7-Tesla Mri To Derive Quantitative Metrics For The Trigeminal Nerve And Subnuclei Of Limbic Structures In Trigeminal Neuralgia, Judy Alper, Alan C. Seifert, Gaurav Verma, Kuang-Han Huang, Yael Jacob, Ameen Al Qadi, John W. Rutland, Sheetal Patel, Joshua Bederson, Raj K. Shrivastava, Bradley N. Delman, Priti Balchandani

Publications and Research

Background: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal …

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 …

Intra-Arterial Combination Therapy For Experimental Acute Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Amanda A. Gorman, Gregory J. Bix, Justin F. Fraser

Neurosurgery Faculty Publications

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra-arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra-arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L-type calcium channels, whereas lubeluzole, …

Microrna-146a-5p, Neurotropic Viral Infection And Prion Disease (Prd), Aileen I. Pogue, Walter J. Lukiw

School of Graduate Studies Faculty Publications

The human brain and central nervous system (CNS) harbor a select sub-group of potentially pathogenic microRNAs (miRNAs), including a well-characterized NF-kB-sensitive Homo sapiens microRNA hsa-miRNA-146a-5p (miRNA-146a). miRNA-146a is significantly over-expressed in progressive and often lethal viral- and prion-mediated and related neurological syndromes associated with progressive inflammatory neurodegeneration. These include ~18 different viral-induced encephalopathies for which data are available, at least ~10 known prion diseases (PrD) of animals and humans, Alzheimer’s disease (AD) and other sporadic and progressive age-related neurological disorders. Despite the apparent lack of nucleic acids in prions, both DNA- and RNA-containing viruses along with prions significantly induce miRNA-146a …

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …

Smoking-Induced Sex Differences In Clinical Outcomes In Patients Undergoing Mechanical Thrombectomy For Stroke, Jacqueline A. Frank, Kara Jo Swafford, Jill M. Roberts, Amanda L. Trout, Ann M. Stowe, Douglas E. Lukins, Stephen Grupke, Keith R. Pennypacker, Justin F. Fraser

Neurology Faculty Publications

OBJECTIVE: Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke.

METHODS: Subjects (N = 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Explicit Training To Improve Affective Prosody Recognition In Adults With Acute Right Hemisphere Stroke, Alexandra Zezinka Durfee, Shannon M. Sheppard, Erin L. Meier, Lisa Bunker, Erjia Cui, Ciprian Crainiceanu, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Difficulty recognizing affective prosody (receptive aprosodia) can occur following right hemisphere damage (RHD). Not all individuals spontaneously recover their ability to recognize affective prosody, warranting behavioral intervention. However, there is a dearth of evidence-based receptive aprosodia treatment research in this clinical population. The purpose of the current study was to investigate an explicit training protocol targeting affective prosody recognition in adults with RHD and receptive aprosodia. Eighteen adults with receptive aprosodia due to acute RHD completed affective prosody recognition before and after a short training session that targeted proposed underlying perceptual and conceptual processes. Behavioral impairment and lesion characteristics were …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …

Headache And Its Association With Adhd/Add And Stimulant Medication, Claire Nitzsche

Honors Scholar Theses

Years of research has shown that headache (in terms of frequency, duration, and severity) is perpetuated by dysregulation of lifestyle behaviors such as sleep habits, eating habits, level of stress, physical activity etc. Our project aims to explore the potential combined and independent impacts that having ADHD/ADD and taking stimulant drugs have on disrupting one’s lifestyle and examine whether dysregulated lifestyle behaviors contribute to one’s headache experience. No research has investigated how both ADHD/ADD and stimulant drug use effect headache experience. In this cross-sectional study, 177 UConn undergraduate students completed a 10-minute survey regarding lifestyle behaviors and headache experience. Participants …

Dabigatran Reduces Thrombin-Induced Neuroinflammation And Ad Markers In Vitro: Therapeutic Relevance For Alzheimer's Disease, Syed Waseem Bihaqi, Haripriya Vittal Rao, Abhik Sen, Paula Grammas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Vascular risk factors such as atherosclerosis, diabetes, and elevated homocysteine levels are strongly correlated with onset of Alzheimer's disease (AD). Emerging evidence indicates that blood coagulation protein thrombin is associated with vascular and non-vascular risk factors of AD. Here, we examined the effect of thrombin and its direct inhibitor dabigatran on key mediators of neuro-inflammation and AD pathology in the retinoic acid (RA)-differentiated human neuroblastoma cell line SH-SY5Y. Methods: SH-SY5Y cells exposed to thrombin concentrations (10–100 nM) +/- 250 nM dabigatran for 24 h were analyzed for protein and gene expression. Electrophoretic mobility shift assay (EMSA) was used to …

Cross-Sectional Exploration Of Plasma Biomarkers Of Alzheimer's Disease In Down Syndrome: Early Data From The Longitudinal Investigation For Enhancing Down Syndrome Research (Life-Dsr) Study, James A. Hendrix, David C. Airey, Angela Britton, Anna D. Burke, George T. Capone, Ronelyn Chavez, Jacqueline Chen, Brian Chicoine, Alberto C. S. Costa, Jeffrey L. Dage, Eric Doran, Anna Esbensen, Casey L. Evans, Kelley M. Faber, Tatiana M. Foroud, Sarah Hart, Kelsey Haugen, Elizabeth Head, Suzanne Hendrix, Hampus Hillerstrom, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ_1-40, Aβ_1-42), and glial fibrillary acidic protein (GFAP) were undertaken with …

A Systematic Review And Meta-Analysis On The Efficacy Of Repeated Transcranial Direct Current Stimulation For Migraine, Guoshuai Cai, Zhu Xia, Leigh Charvet, Feifei Xiao, Abhishek Datta, X Michelle Androulakis

Publications and Research

Purpose: Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine.

Methods: In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities.

Results: Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of …

Gait And Balance Changes With Investigational Peripheral Nerve Cell Therapy During Deep Brain Stimulation In People With Parkinson’S Disease, Geetanjali Gera, Zain Guduru, Tritia R. Yamasaki, Julie A. Gurwell, Monica Chau, Anna Krotinger, Frederick A. Schmitt, John T. Slevin, Greg A. Gerhardt, Craig G. Van Horne, Jorge E. Quintero

Physical Therapy Faculty Publications

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the …

Method Of Intra-Arterial Drug Administration In A Rat: Sex Based Optimization Of Infusion Rate, Sarah J. Messmer, Justin F. Fraser, Keith R. Pennypacker, Jill M. Roberts

Center for Advanced Translational Stroke Science Faculty Publications

BACKGROUND: Endovascular thrombectomy is the process of removing a blood clot and re-establishing blood flow in patients with emergent large vessel occlusion. The technique provides an opportunity to deliver therapeutics directly to the site of injury. The intra-arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. Here, we adapted the IA method for use in rats, by investigating various flow rates to optimize the IA injection through the internal carotid artery (ICA).

METHODS: Male and female Sprague-Dawley rats (∼4 months of age) were subjected to placement …

Space-Occupying Brain Lesions, Trauma-Related Tau Astrogliopathy, And Artag: A Report Of Two Cases And A Literature Review, Adam D. Bachstetter, Filip G. Garrett, Gregory A. Jicha, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age-affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the …

Differential Leukocyte And Platelet Profiles In Distinct Models Of Traumatic Brain Injury, William Brad Hubbard, Meenakshi Banerjee, Hemendra J. Vekaria, Kanakanagavalli Shravani Prakhya, Smita Joshi, Qingjun Wang, Kathryn E. Saatman, Sidney W. Whiteheart, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) …

CertL Reduces C16 Ceramide, Amyloid-Β Levels, And Inflammation In A Model Of Alzheimer’S Disease, Simone M. Crivelli, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Daan Van Kruining, Gerard Bode, Sandra Den Hoedt, Barbara Hobo, Anna-Lena Scheithauer, Jochen Walter, Monique T. Mulder, Christopher Exley, Matthew Mold, Michelle M. Mielke, Helga E. De Vries, Kristiaan Wouters, Daniel L. A. Van Den Hove, Dusan Berkes, María Dolores Ledesma, Joost Verhaagen, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.

METHODS: A plasmid expressing CERT_L, the long isoform of CERTs, was used to study the interaction of CERT_L with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERT_L protein …

Aberrant Maturation Of The Uncinate Fasciculus Follows Exposure To Unpredictable Patterns Of Maternal Signals, Steven J. Granger, Laura M. Glynn, Curt A. Sandman, Steven L. Small, Andre Obenaus, David B. Keator, Tallie Z. Baram, Hal S. Stern, Michael A. Yassa, Elyssia Poggi Davis

Psychology Faculty Articles and Research

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother–child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key …

Machine Intelligence Identifies Soluble Tnfa As A Therapeutic Target For Spinal Cord Injury, J. R. Huie, A. R. Ferguson, N. Kyritsis, J. Z. Pan, K.-A. Irvine, J. L. Nielson, P. G. Schupp, M. C. Oldham, John C. Gensel, A. Lin, M. R. Segal, R. R. Ratan, J. C. Bresnahan, M. S. Beattie

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five …

Assessment Of Major Depressive Disorders Through Neuroimaging Studies And Their Treatment Methods, Jevetha Vijayadasan, Diksha Raghunathan, Sivakumar Rajagopal, Rahul Soangra

Physical Therapy Faculty Articles and Research

Many mental disorders are caused due to improper regulation of the brain and depression is one such. It affects both children and adults and is very common among teenagers. There are many challenges clinicians face regarding the management of this disease. These challenges have prompted the development of various neuroimaging techniques that effectively diagnose the condition. The main techniques are Magnetic resonance imaging (MRI) and Positron emission tomography (PET) which have gained momentum over the years. Advanced MRI techniques help study certain regions of the brain such as hippocampus and amygdala. Effective treatments for depression include antidepressant medications and brain …

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

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 …