Nervous System Diseases Commons^™

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

The Role Of Syndecan-1 And Extracellular Vesicles In Breast Cancer Brain Metastasis, Megan R. Sayyad

Theses and Dissertations

Breast cancer metastasizes to the brain in 15-30% of all breast cancer cases, and metastasis is the predominant cause of breast cancer-related deaths. Patients with HER2-enriched and triple-negative breast cancers (TNBCs) are more likely to develop brain metastases. While targeted therapies exist for HER2-enriched breast cancers, there are no effective treatments for TNBCs. Thus, a greater understanding of how these cancers spread to the brain is critical. In order to spread to the brain, disseminated breast cancer cells must overcome 2 major steps—crossing the blood-brain barrier (BBB) and survival and successful colonization of the distinctive and mostly cellular brain environment. …

The Life And Work Of Alex Klein, Ramon Thiago Mendes De Oliveira

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alex Klein is one of the best-known figures of the American oboe school. He is the winner of multiple international competitions, including the first prize at the Geneva’s Concours International d’Execution Musicale. Appointed principal oboe at the Chicago Symphony Orchestra in 1995, Klein is one of the most highly regarded musicians hired during the Barenboim era. His recording of Richard Strauss’ oboe concerto with the CSO was awarded Best Instrumental Soloist Performance (with Orchestra) at the 44th Grammy Awards. In 2004, his tenure at CSO was interrupted due to the onset of Focal Dystonia; which affected multiple fingers in …

Implementation Of Stroke Pathways To Reduce Length Of Stay, Cost, Readmissions, And Mortality, Jayme Strauss, Daniel Hartnett, Jenny Ductant, Peter De Armas, Albert Fernandez, Andrew Waisbrot, Amy Starosciak, Felipe De Los Rios La Rosa

All Publications

No abstract provided.

Addressing Stroke Patient And Family Reasons For Not Calling 911, Maygret Ramirez, Rodney Bedgio, Virginia Ramos, Ivis Gonzalez, Yaima Miro Gonzalez, Amy Starosciak, Daniel D'Amour, Jayme Strauss, Felipe De Los Rios La Rosa

All Publications

No abstract provided.

Role Of Sarm1 In Chronic Immune-Mediated Central Nervous System Inflammation, Kenneth E. Viar Ii

Theses and Dissertations

SARM1 is an injury-induced nicotinamide adenine dinucleotide nucleosidase (NADase) that was previously shown to promote axonal degeneration in response to traumatic, toxic, and excitotoxic stressors. This raises the question of whether a SARM1-dependent program of axonal degeneration is central to a common pathway contributing to disease burden in neurological disorders. The degree to and mechanism by which SARM1 inactivation decreases the pathophysiology of such disorders is of interest to establish the rationale to pursue SARM1 as a therapeutic target. In this study, we compare the course and pathology of experimental autoimmune encephalomyelitis (EAE) in Sarm1-knockout (KO) mice and wild-type …

Long-Term Effects Of Notch1 Signaling On Neural Stem Cells Following Traumatic Brain Injury, Cruz Sevilla Jr

Theses and Dissertations

Traumatic brain injury (TBI) is a devastating problem which stands as a leading cause of death and disability. The elderly is significantly affected by TBI, typically as the result of falls, and recovery is especially limited. This, in part, is associated with decreased tissue-specific stem cell regeneration and replacement of damaged cells in the aged brain. The diminished ability of the aged brain to recover is especially devastating after TBI, likely leading to permanent loss of sensory, motor, and cognitive functions. Studies have shown that the mature mammalian brain contains Neural Stem Cells (NSCs), found in specific regions of the …

Roche Announces U.S., Canada Sites For Phase 3 Clinical Trial Of Huntington's Disease Drug, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Building Solidarity In Disease Communities’ Quest For Better Care And Treatments: A Conversation With A Young Tennis Award-Winner, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Early Identification Of Depression In Patients With Pediatric Epilepsy, Erin Fecske, Paul Glasier, Lines Vargas Collado, Elizabeth Rende

Posters

Describes the use of the Neurological Disorders Depression Inventory-Epilepsy-Youth (NDDI-E-Y) in adolescent patients in a comprehensive epilepsy center to identify patients who need referral for mental health care.

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Protein Aggregates And Polyglutamine Tracts In Neurodegenerative Disease, John Mack

Senior Honors Theses

The incidence of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and other Polyglutamine Diseases is projected to dramatically increase throughout the developed world, and yet the pathology of these diseases remains poorly understood. One pathway that these neurodegenerative diseases share is the accumulation of pathologic proteins which are not only harmful in their soluble form but may go on to form toxic aggregates. In many cases, a consensus has yet to be reached concerning the mechanism for protein aggregation. Therefore, the exploration of the roles of these proteins and their possible mechanisms, along with potential techniques for …

This Thanksgiving, Appreciating Stable Health And New Plans For Huntington's Disease Advocacy, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Who Did It?: A Review On The Possible Causes Of Multiple Sclerosis, Mia Difrancesco

D.U.Quark

Multiple Sclerosis (MS) is an incurable autoimmune disorder that attacks the myelin sheath surrounding nerve cells. Steady demyelination of these cells over time results in painful inflammation and reduced mobility. Genetic abnormalities could be responsible for the onset of this disease. Chromosomal mutations found in MS patients as well as environmental factors influencing the expression of certain genes will be analyzed in this review. Moreover, treatments regulating gene expression in MS patients will be discussed. Further genetic research would not only provide scientists and medical professionals with a deeper understanding of MS and other autoimmune disorders, but also lead to …

Roche Announces First Sites For Key Huntington’S Disease Observational Study, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

A Real World Experience Of The Fast-Ed Based Pre-Hospital Stroke Triage System To Detect Large Vessel Occlusions, Ned Shashoua, Amy Starosciak, Jayme Strauss, Felipe De Los Rios La Rosa

All Publications

No abstract provided.

Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru Iacobas, Libor Velisek

NYMC Faculty Publications

Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the …

Unpacking Generation Hd1, The Roche Phase 3 Huntington's Disease Clinical Trial, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Roche Phase 3 Clinical Trial For Huntington’S Disease Gene-Slicing Drug To Enroll Volunteers In Early 2019, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …

Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic

Epidemiology and Environmental Health Faculty Publications

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.

Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).

Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.

Results: We observed significant methylation differences in …

Changes In The Testes Following Spinal Cord Injury And The Attenuating Effects Of Licofelone, Ryan Fortune

Dissertations and Theses (Open Access)

Spinal cord injury is a devastating disease that researchers have had very limited success in treating. In addition to interrupted innervation, spinal cord injury causes pathologic changes in a multitude of organ systems. Male infertility is one such complication that is particularly devastating because the patient population is predominantly young men. Our lab has previously shown that the blood testis barrier breaks down after spinal cord injury. This dissertation shows the local metabolomic and mRNA changes that spinal cord injury causes within the testes using a Sprague Dawley rat model, including the elevation in eicosanoids, increased oxidative stress, chronically elevated …

Predicting Gains With Visuospatial Training After Stroke Using An Eeg Measure Of Frontoparietal Circuit Function, Robert J. Zhou, Hossein M. Hondori, Maryam Khademi, Jessica M. Cassidy, Katherine M. Wu, Derek Z. Yang, Nikhita Kathuria, Fareshte R. Erani, Lucy Dodakian, Alison Mckenzie, Cristina V. Lopes, Walt Scacchi, Ramesh Srinivasan, Steven C. Cramer

Physical Therapy Faculty Articles and Research

The heterogeneity of stroke prompts the need for predictors of individual treatment response to rehabilitation therapies. We previously studied healthy subjects with EEG and identified a frontoparietal circuit in which activity predicted training-related gains in visuomotor tracking. Here we asked whether activity in this same frontoparietal circuit also predicts training-related gains in visuomotor tracking in patients with chronic hemiparetic stroke. Subjects (n = 12) underwent dense-array EEG recording at rest, then received 8 sessions of visuomotor tracking training delivered via home-based telehealth methods. Subjects showed significant training-related gains in the primary behavioral endpoint, Success Rate score on a standardized test …

In Harriet’S Tragic Death, The Vulnerability Caused By Huntington's Disease – But Also The Story Of A Beautiful Soul, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung

PRECS 2018

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and …

The Combination Of Human Urinary Kallidinogenase And Mild Hypothermia Protects Adult Rats Against Hypoxic-Ischemic Encephalopathy-Induced Injury By Promoting Angiogenesis And Regeneration, Xiaoya Gao, Haiting Xie, Shuzhen Zhu, Bin Yu, Ying Xian, Penghua Wang, Qing Wang

NYMC Faculty Publications

Objectives: Human Urinary Kallidinogenase (HUK) is a tissue kallikrein that plays neuroprotective role in ischemic conditions via different mechanisms. Mild hypothermia (MH) is another robust neuroprotectant that reduces mortality but does not profoundly ameliorate the neurological outcome in hypoxic-ischemic encephalopathy (HIE) patients. However, whether the combination of HUK and MH can be used as a promising neuroprotective treatment in HIE is unknown. Methods: One-hundred and forty-four adult Wistar rats were randomly divided into five groups: Sham, HIE, HUK, MH and a combination of HUK and MH treatment. The HIE rat model was established by right carotid dissection followed by hypoxia …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller

Anatomy and Regenerative Biology Faculty Publications

Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal …