Nervous System Diseases Commons^™

Ion Channel Candidates Mediating Orexin Neuropeptide Actions On Brainstem Serotonergic Neurons, Saqlain Javed

NYMC Student Theses and Dissertations

A loss of neurons that synthesize the neuropeptide orexin produces the sleep disorder narcolepsy with cataplexy in humans and other animals. How symptoms of this disorder arise is not well understood, but selectively restoring orexin actions at 5-HT DR neurons rescues key symptoms (cataplexy), suggesting normal orexin signaling is important at these neurons. To better understand how orexin acts on these neurons, our lab identified a set of novel orexin actions that appear mediated by unidentified cation- permeable ion channels. To narrow down the list of possible channels, we used a bioinformatics approach to compare published gene expression profiles of …

A Bird's-Eye View Of The Multiple Biochemical Mechanisms That Propel Pathology Of Alzheimer's Disease: Recent Advances And Mechanistic Perspectives On How To Halt The Disease Progression Targeting Multiple Pathways., Caleb Vegh, Kyle Stokes, Dennis Ma, Darcy Wear, Jerome Cohen, Sidhartha D. Ray, Siyaram Pandey

Touro College of Pharmacy (New York) Publications and Research

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including …

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 …

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 …

Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, Shankar J. Chinta, Georgia Woods, Marco Demaria, Anand Rane, Ying Zou, Amanda Mcquade, David T. Madden

Faculty Publications & Research of the TUC College of Pharmacy

Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against …

Is Detection Of Preclinical Alzheimer’S Disease Possible?, Shana Brawer

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Molecular Mechanisms Of Alzheimer’S Disease, Abraham Bordon

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease was first discovered in 1906 by Alois Alzheimer. It is a neurodegenerative disease characterized by the buildup of toxic amyloid plaque and intracellular neurofibrillary tangles, which results in the progressive loss of cognitive function and memory. Since its discovery, the disease has become a growing health concern, particularly in the developed world, where the ageing demographics have contributed to an increase in its prevalence and incidence. The earliest research into the disease focused on neurochemical analyses and resulted in the formulation of the cholinergic hypothesis. The mechanism of disease was explained as the degeneration of the cholinergic system …

Possible Causes Of Alzheimer’S Disease Related Amyloid-Β Plaques And Neurofibrillary Tangles, Rochelle Rubenstein

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a major cause of dementia in the elderly and is a global health concern. However, researchers are not sure what causes the characteristic amyloid-β plaque accumulation and neurofibrillary tangles in the brain. Several model mechanisms have been proposed to answer this question. This paper examines three of these possibilities. Research suggests that a particular allele of the apoE gene is responsible for the neurodegeneration found in Alzheimer’s disease. Another hypothesis is that the mechanism of Alzheimer’s is related to prion-mediated protein misfolding. Other studies indicate that certain environmental factors can cause the neuropathology of Alzheimer’s. Specifically, this …

Repurposing Diabetes Drugs To Treat Insulin Resistance In Alzheimer’S Disease‌, Yael Lazarus

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative condition which results in a significant decline in cognitive status. Novel treatment approaches for Alzheimer’s are sorely needed, as current medications for the disease offer only marginal clinical benefit. Research has discovered a connection between the pathology of Alzheimer’s and Type 2 Diabetes, two serious and seemingly unrelated disorders. Clinical studies have shown that Alzheimer’s disease is associated with brain insulin resistance similar to the pathology of Type 2 Diabetes. This observation has led to the notion that drugs developed for the treatment of Type 2 Diabetes may be beneficial in modifying the cognitive function …

Luteinizing Hormone And Alzheimer’S Disease: Impact And Possibilities Of Treatment, Rachel Walkin

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a common neurodegenerative disease that is the 6th leading cause of death in the United States. An estimated 5 million Americans are afflicted nationwide and the cost to the economy is valued at 259 billion dollars. Additionally, unlike other major causes of death in the United States, there is no treatment for Alzheimer’s Disease. Alzheimer’s is a progressive disease and it is strongly tied to aging. In most cases symptoms make their first appearance in the late 60’s and gradually worsen, eventually leading to a loss of cognitive function and death. The two outstanding changes in the …

Anti-Inflammatory And Neuroprotective Role Of Natural Product Securinine In Activated Glial Cells: Implications For Parkinson’S Disease, Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J. Lithgow, Julie K. Andersen, Shankar J. Chinta

Faculty Publications & Research of the TUC College of Pharmacy

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects …

Single Low-Dose Lipopolysaccharide Preconditioning: Neuroprotective Against Axonal Injury And Modulates Glial Cells, Ryan C. Turner, Zachary J. Naser, Brandon P. Lucke-Wold, Aric F. Logsdon, Reyna L. Vangilder, Rae Reiko Matsumoto, Jason D. Huber

Faculty Publications & Research of the TUC College of Pharmacy

AIM: Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear.

METHODS: The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely …

Meta Analysis Of Human Alzgene Database: Benefits And Limitations Of Using C. Elegans For The Study Of Alzheimer's Disease And Co-Morbid Conditions, Behrad Vahdati Nia, Christine Kang, Michelle G. Tran, Deborah Lee, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Human genome-wide association studies (GWAS) and linkage studies have identified 695 genes associated with Alzheimer's disease (AD), the vast majority of which are associated with late-onset AD. Although orthologs of these AD genes have been studied in several model species, orthologs in the nematode, Caenorhabditis elegans, remain incompletely identified, with orthologs to only 17 AD-related genes identified in the C. elegans database, WormBase. Therefore, we performed a comprehensive search for additional C. elegans orthologs of AD genes using well-established programs, including OrthoList, which utilizes four ontology prediction programs. We also validated 680 of the AD genes as a unique …

Spinal Epidural Abscess Complicated By Meningitis, Sepsis And Thrombocytopenia In A Patient Lacking Traditional Risk Factors, Christian Spano, Michael Ward, Nicole Zagelbaum

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Spinal epidural abscess is a rare diagnosis with a classic triad of fever, spinal pain and neurologic deficits. Only a small proportion of patients have all three findings, making the diagnosis challenging. Here we present a case of cervical and thoracic spinal epidural abscess complicated by meningitis, sepsis and thrombocytopenia in a patient lacking traditional risk factors. The patient was initially treated non-operatively secondary to thrombocytopenia but subsequently required transfer to a tertiary care facility for surgical drainage after clinical deterioration. This case report highlights the need for a high index of suspicion and low threshold for imaging when considering …

Cyclophosphamide For Suspected Primary Angiitis Of The Central Nervous System In A Patient With Human Immunodeficiency Virus: A Case Report, Martha M. Rumore, Samantha Su, Jake Pellinen

Touro College of Pharmacy (New York) Publications and Research

Introduction: Central nervous system (CNS) vasculitis is rare, including in human immunodeficiency virus (HIV), occurring in less than 1% of patients. Systemic vasculitis affecting the CNS is termed secondary CNS vasculitis, whereas primary CNS vasculitis, referred to as primary angiitis of the CNS (PACNS) refers to an extremely rare disease specifically confined to the CNS. Only some cases of PACNS in HIV patients have been reported in literature.

Case Report: We report a case of a 46-year-old female with HIV who developed probable primary CNS vasculitis, which was treated with intravenous cyclophosphamide and glucocorticoids for both induction and …

Is Deep Brain Stimulation A Viable Treatment For Parkinson’S Disease?, Brocha Gold

The Science Journal of the Lander College of Arts and Sciences

Treatment options for those suffering from Parkinson’s Disease are as diverse as its symptoms. With the advent of modern technology there are new and innovative treatments that are becoming available, such as Deep Brain Stimulation (DBS). Prior to exploring treatment options one must understand the various causes of the disease. Treatment of the various motor and non-motor symptoms can include a combination of medication and surgical therapies. Among surgical interventions DBS is the treatment of choice. It has the fewest side effects and provides the greatest symptomatic relief.

The Influence Of Solid Microneedles On The Transdermal Delivery Of Selected Antiepileptic Drugs, Julia Nguyen, Kevin B. Ita, Matthew J. Morra, Inna E. Popova

Faculty Publications & Research of the TUC College of Pharmacy

The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm²/h) compared to passive delivery (12.83 ± 6.30 µg/cm …

Marijuana Compounds: A Nonconventional Approach To Parkinson’S Disease Therapy, Mariana Babayeva, Haregewein Assefa, Paramita Basu, Sanjeda Chumki, Zvi G. Loewy

Touro College of Pharmacy (New York) Publications and Research

Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency.This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review …

Editorial: Biology Of Cognitive Aging: Model Systems, Technologies, And Beyond, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

The author provides an introduction to a research issue of Frontiers in Genetics on models and techniques related to age-related memory impairment.

Time Of Day And Performance On Cognitive Tests In Patients With Mild Dementia, Upinder Singh, Mandeep Gill, Rebecca Rice, Fallon Dimaano, Andrea Warburton, Michael R. Wells

College of Osteopathic Medicine (TUN) Publications and Research

Background

Cognitive screening for elderly patients with mild dementia is typically conducted in the morning under the impression that testing at this time will optimize performance and cooperation of patients. This study was conducted to determine if the time of day in which several cognitive screening tests would be normally given could significantly affect test performance in patients with mild dementia and normal control subjects.

Methods

Fifty nursing home residents with mild to moderate dementia and twenty normal control subjects were given three commonly used cognitive tests in two separate sessions (morning and afternoon) with a two week interval between …

Assessment Of Three Acute Responses To Traumatic Brain Injury, Shoshana Fireworker

The Science Journal of the Lander College of Arts and Sciences

Traumatic brain injury has a devastating effect on millions worldwide each year. As yet, there are no methods which have been proven to improve recovery from the trauma. Current treatment protocols revolve around reducing secondary insult, such as hypoxia, hypotension, and cerebral edema, which raises intracranial pressure. The purpose of this study is to assess the efficacy of three responses to traumatic brain injury. Two of them, the administration of hypertonic saline and the administration of progesterone, are pharmacologic, while the third, the performance of a decompressive craniectomy, is surgically invasive. A number of original studies have been analyzed to …

Creutzfeldt-Jakob Disease And Alzheimer’S Disease: Does Overlap Of Mechanism Mean Overlap Of Treatment Methods?, David Rotblat

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative disorder that is the 6th leading cause of death in the United States. More than 5.5 million People over the age of 65 are currently diagnosed with Alzheimer’s disease with predictions of 13.8 million to be diagnosed by the year 2050 (Sultana, et al., 2013) (Hebert, Weuve, Scherr, & Evans, 2013). With few treatments available, scientists are desperately looking for a solution to this growing epidemic. Creutzfeldt-Jakob disease is also a neurodegenerative disorder, but with a far less prevalence of only 4.6 persons per million per year. It was discovered that Alzheimer’s and Creutzfeldt-Jakob disease …

Role Of Sigma-1 Receptors In Neurodegenerative Diseases, Linda Nguyen, Brandon P. Lucke-Wold, Shona A. Mookerjee, John Z. Cavendish, Matthew J. Robson, Anna L. Scandinaro, Rae Reiko Matsumoto

Faculty Publications & Research of the TUC College of Pharmacy

Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In …

Is There A Link Between Saturated Fat Intake And Alzheimer’S Disease?, Justin Konig

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative disease that causes dementia and ultimately death. Currently, there is no treatment available for this disease. The aging of the population will only increase the incidence of Alzheimer’s disease, making it ever more important to find an effective method of prevention. Dietary intervention is a practical and affordable method of intervention. The brain is a fat rich organ, and dietary fats are critical for proper development of the brain. A literature review was conducted to determine whether there is a link between saturated fat intake and Alzheimer’s disease. According to the literature reviewed, saturated fat …

Amyotrophic Lateral Sclerosis (Als) And Spinal Muscular Atrophy (Sma): A Genetic Linkage?, Michael Groden

The Science Journal of the Lander College of Arts and Sciences

Neurodegenerative motor neuron disorders (MNDs) have devastating effects. Spinal Muscular Atrophy (SMA), for example, is a debilitating and sometimes lethal disease in children. SMA is monogenic, autosomal recessively inherited disorder caused by a loss-of-function mutation of surviving motor neuron 1 (SMN1). SMN2 is an identical copy of this gene and produces abbreviated transcripts without exon 7 though some full transcripts are produced that ameliorate the disease. Previous clinical trials for this disease have not produced consistent results. However, in a recent cross-sectional study, biomarkers for SMA (BforSMA), protein candidates and metabolite markers were identified (Finkel et al., 2012). These markers …

Treating Acute Migraines: Triptans Vs. Antiemetics, Samuel Reisman

The Science Journal of the Lander College of Arts and Sciences

Influential American medical organizations and publications have published guidelines for the treatment of acute migraine headaches that omit antiemetics, usually suggesting triptans as the first line of treatment. A review of the few comparative studies directly contrasting clinical outcomes of triptans and antiemetics in the treatment of acute migraines suggest that both treatment options are relatively equal in efficaciousness. The added burden of triptan usage, including an added risk of adverse effects and a high cost per dose, would seem to warrant an antiemetic-first approach to migraine treatment, as recommended by several international health communities. Possible reasons for the prominent …

Efficacy Of A Carbon Fiber Orthotic Toe-Off Brace In Adults With Cerebral Palsy, June Kume, John R. Magel, Erin Dicandia, Justine Hoffman, Robert Issing, Joshua Little, Tyler Roden

The School of Health Sciences Publications and Research

Purpose/Hypothesis : This pilot study evaluated the effects of a unique carbon fiber ankle/foot orthosis for individuals diagnosed with foot drop (“Toe-Off” design, Allard USA, Inc). We hypothesized that use of this brace would be useful for adults with cerebral palsy (CP) as evidenced by improved gait characteristics including gait endurance and balance.

Number of Subjects : A convenience sample of 4 patients, between the ages of 29 and 55, with diagnoses of cerebral palsy, was successfully recruited from United Cerebral Palsy (UCP) of Suffolk (Central Islip, NY). All individuals received regular physical therapy at UCP prior to and throughout …

Neural Plasticity Following Ischemia, Shira Brickman

The Science Journal of the Lander College of Arts and Sciences

Neural plasticity refers to the ability of one’s brain to change its structure and/or function in response to changes in behavior, environment, and neural processes. When a person suffers an ischemic brain injury, it often leads to hemisyndrome with motor and sensory deficits in the arm, leg, and face of one side. This article discusses the various ways that the existing network can be restructured and neuronal connections can be remodeled after the injury to enable partial or complete recovery of motor function. Spontaneous functional recovery after stroke develops through the overlapping sequence of events including a phase of axonal …

Prosopagnosia, Leah Fleischman

The Science Journal of the Lander College of Arts and Sciences

Prosopagnosia is a cognitive disorder that affects one’s ability to recognize faces. Prosopagnosia can be caused by a congenital defect, or it can be acquired as a result of brain damage. Much research has been devoted to discovering the specific causes and effects of Prosopagnosia. Many case studies have been performed in order to determine the specific effects that each case of Prosopagnosia causes for various individuals suffering from the disease. This article discusses the various aspects of Prosopagnosia; specifically focusing on the behavioral, anatomical, and neurological implications

Stem Cells As A Cure For Amyotrophic Lateral Sclerosis, Chaya K. Hirsch

The Science Journal of the Lander College of Arts and Sciences

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease which affects approximately 30,000 Americans at any given time (alsa.org, 2010). The etiology of this terminal disease unfortunately remains an unsolved mystery and has therefore severely limited the ability to find a cure. The use of stem cells to regenerate neurons has been vastly studied and have produced very promising results. However, its practicality as a cure or treatment for neurodegenerative diseases, such as ALS, is greatly compromised. Three different therapies involving stem cells were examined, Embryonic Stem Cells (ESC), induced pluripotent stem cells, (iPSC) and direct reprogramming of adult …