Neuroscience and Neurobiology Commons^™

Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya

Publications

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count …

Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Publications and Research

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …

Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker

Neurology Faculty Publications

Background: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.

Methods: Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or …

New Functions For The Proprioceptive System In Skeletal Biology, Ronen Blecher, Lia Heinemann-Yerushalmi, Eran Assaraf, Nitzan Konstantin, Jens R. Chapman, Timothy C. Cope, Guy S. Bewick, Robert W. Banks, Elazar Zelzer

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle spindles and Golgi tendon organs (GTOs) are two types of sensory receptors that respond to changes in length or tension of skeletal muscles. These mechanosensors have long been known to participate in both proprioception and stretch reflex. Here, we present recent findings implicating these organs in maintenance of spine alignment as well as in realignment of fractured bones. These discoveries have been made in several mouse lines lacking functional mechanosensors in part or completely. In both studies, the absence of functional spindles and GTOs produced a more severe phenotype than that of spindles alone. Interestingly, the spinal curve phenotype, …

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

Metabolic And Vascular Imaging Biomarkers In Down Syndrome Provide Unique Insights Into Brain Aging And Alzheimer Disease Pathogenesis, Elizabeth Head, David K. Powell, Frederick A. Schmitt

Pharmacology and Nutritional Sciences Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD). Neuropathology consistent with AD is present by 40 years of age and dementia may develop up to a decade later. In this review, we describe metabolic and vascular neuroimaging studies in DS that suggest these functional changes are a key feature of aging, linked to cognitive decline and AD in this vulnerable cohort. FDG-PET imaging in DS suggests systematic reductions in glucose metabolism in posterior cingulate and parietotemporal cortex. Magentic resonance spectroscopy studies show consistent decreases in neuronal health and increased myoinositol, suggesting inflammation. There are …

Myelin As An Inflammatory Mediator: Myelin Interactions With Complement, Macrophages, And Microglia In Spinal Cord Injury, Timothy J. Kopper, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of activated resident and infiltrating immune cells (especially microglia/macrophages). The environmental factors contributing to this protracted inflammation are not well understood; however, myelin lipid debris is a hallmark of SCI. Myelin is also a potent macrophage stimulus and target of complement‐mediated clearance and inflammation. The downstream effects of these neuroimmune interactions have the potential to contribute to ongoing pathology or facilitate repair. This depends in large part on whether myelin drives pathological or reparative macrophage activation states, commonly referred to as M1 (proinflammatory) or M2 (alternatively) macrophages, respectively. Here we review …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

Historical And Cross-Cultural Perspectives On Parkinson's Disease, Lee Xenakis Blonder

Sanders-Brown Center on Aging Faculty Publications

Parkinson’s disease (PD) is a common neurodegenerative disorder, affecting up to 10 million people worldwide according to the Parkinson’s Disease Foundation. Epidemiological and genetic studies show a preponderance of idiopathic cases and a subset linked to genetic polymorphisms of a familial nature. Traditional Chinese medicine and Ayurveda recognized and treated the illness that Western Medicine terms PD millennia ago, and descriptions of Parkinson’s symptomatology by Europeans date back 2000 years to the ancient Greek physician Galen. However, the Western nosological classification now referred to in English as “Parkinson’s disease” and the description of symptoms that define it, are accredited to …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations and Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Global Burden Of Neuroendocrine Tumors And Changing Incidence In Kentucky, Aman Chauhan, Qian Yu, Neha Ray, Zainab Farooqui, Bin Huang, Eric B. Durbin, Thomas Tucker, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

Background: Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data.

Methods: KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data …

The Dynamics Of Concussion: Mapping Pathophysiology, Persistence, And Recovery With Causal-Loop Diagramming, Erin S. Kenzie, Elle L. Parks, Erin D. Bigler, David W, Wright, Miranda M. Lim, James C. Chesnutt, Gregory W.J. Hawryluk, Wayne Gordon, Wayne Wakeland

Complex Systems Faculty Publications and Presentations

Concussion, also known as mild traumatic brain injury (mTBI),1 is a significant public health issue responsible for a variety of cognitive, emotional, and somatic symptoms and deficits (3). It is unclear why some individuals appear to recover relatively quickly while others suffer prolonged symptoms and impairments (4–7). Robust clinical means of diagnosis, prognosis, and treatment are also lacking (8–11). Research is hindered by an inadequate classification system for traumatic brain injury (TBI) (12), “poor” study quality (13, 14), disagreement about appropriate inclusion and exclusion criteria for concussion (8, 15), and an incomplete understanding of underlying pathophysiology (16–18). The heterogeneity and …

Calnexin Is Necessary For T Cell Transmigration Into The Central Nervous System, Amber M. Paul, Joanna Jung, Paul Eggleton, Alison Robinson, Jessica Wang, Nick Gutowski

Publications

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune …

Immune Checkpoint Inhibitors In Large Cell Neuroendocrine Carcinoma: Current Status, Aman Chauhan, Susanne Arnold, Jill M. Kolesar, Hala Elnakat Thomas, B. Mark Evers, Lowell B. Anthony

Markey Cancer Center Faculty Publications

Introduction: Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors that often behave clinically like small cell carcinoma (SCLC) and are treated as such. No major advancement in the management of these tumors has occurred in the last 30 years.

Methods: We present a case series of three cases from Markey Cancer center along with a review of 13 published cases in the literature wherein immune-checkpoint inhibitors were utilized in the management of LCNEC.

Results: Immune-checkpoint inhibitors might have clinical activity in LCNEC.

Conclusion: Role of immune-checkpoint inhibitors should be explored in prospective LCNEC clinical …

Lafora Disease Offers A Unique Window Into Neuronal Glycogen Metabolism, Matthew S. Gentry, Joan J. Guinovart, Berge A. Minassian, Peter J. Roach, Jose M. Serratosa

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase.

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Mra-Based Evaluation Of Anatomical Variation Of Circle Of Willis In Adult Pakistanis, Rehana Shaikh, Saba Sohail

Department of Radiology

Objective: To determine the frequency and patterns of normal anatomical variation of Circle of Willis on magnetic resonance angiogram in adults without cerebrovascular disease.
Methods: This descriptive cross-sectional study was conducted at the Radiology Department of Dow University of Health Sciences / Civil Hospital, Karachi, from January to December 2016, and comprised patients referred for magnetic resonance imaging of the brain and magnetic resonance angiogram without any clinical or radiological manifestation of cerebrovascular disease, primarily including those with suspected demyelination, infection, epilepsy or metastases. Three-dimensional time-of-flight magnetic resonance angiography was performed. The Circle of Willis was assessed for its completeness …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Liposomal Tricurin, A Synergistic Combination Of Curcumin, Epicatechin Gallate And Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, And Eliminates Glioblastoma (Gbm) And Gbm Stem Cells, Sumit Mukherjee, Juliet N. E. Baidoo, Samay Sampat, Andrew Manusco, Lovena David, Leah S. Cohen, Shuiqin Zhou, Probal Banerjee

Publications and Research

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (M): 32:8:100 (termed 32 M+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated …

Internal Carotid Artery Stenosis: A Novel Surgical Model For Moyamoya Syndrome, Jill M. Roberts, Michael E. Maniskas, Justin F. Fraser, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries. There are two forms: Disease and Syndrome, with each characterized by the sub-population it affects. Moyamoya syndrome (MMS) is more prominent in adults in their 20’s-40’s, and is often associated with autoimmune diseases. Currently, there are no surgical models for inducing moyamoya syndrome, so our aim was to develop a new animal model to study this relatively unknown cerebrovascular disease. Here, we demonstrate a new surgical technique termed internal carotid artery stenosis (ICAS), to mimic MMS using micro-coils on the proximal ICA. We tested for …

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects On Neuroinflammation And Synaptic Function Markers In A Mouse Model Of Doxorubicin-Based Chemotherapy, Tonya S. Orchard, Monica M. Gaudier-Diaz, Panchita Phuwamongkolwiwat-Chu, Rebecca Andridge, Maryam B. Lustberg, Joshua Bomser, Rachel M. Cole, Martha A. Belury, Courtney A. Devries

Faculty & Staff Scholarship

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six …

Analytical Cpg Model Driven By Limb Velocity Input Generates Accurate Temporal Locomotor Dynamics, Sergiy Yakovenko, Anton Sobinov, Valeriya Gritsenko

Faculty & Staff Scholarship

The ability of vertebrates to generate rhythm within their spinal neural networks is essential for walking, running, and other rhythmic behaviors. The central pattern generator (CPG) network responsible for these behaviors is well-characterized with experimental and theoretical studies, and it can be formulated as a nonlinear dynam- ical system. The underlying mechanism responsible for locomotor behavior can be expressed as the process of leaky integration with resetting states generating appropriate phases for changing body velocity. The low-dimensional input to the CPG model generates the bilateral pattern of swing and stance modulation for each limb and is consistent with the desired …