Nervous System Diseases Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Altering Endoplasmic Reticulum Stress In A Model Of Blast-Induced Traumatic Brain Injury Controls Cellular Fate And Ameliorates Neuropsychiatric Symptoms, Aric Flint Logsdon, Ryan Coddington Turner, Brandon Peter Lucke-Wold, Matthew James Robson, Zachary James Naser, Kelly Elizabeth Smith, Rae Reiko Matsumoto

Faculty Publications & Research of the TUC College of Pharmacy

Neuronal injury following blast-induced traumatic brain injury (bTBI) increases the risk for neuropsychiatric disorders, yet the pathophysiology remains poorly understood. Blood-brain-barrier (BBB) disruption, endoplasmic reticulum (ER) stress, and apoptosis have all been implicated in bTBI. Microvessel compromise is a primary effect of bTBI and is postulated to cause subcellular secondary effects such as ER stress. What remains unclear is how these secondary effects progress to personality disorders in humans exposed to head trauma. To investigate this we exposed male rats to a clinically relevant bTBI model we have recently developed. The study examined initial BBB disruption using Evan’s blue (EB), …

A Survey Of Oxidative Paracatalytic Reactions Catalyzed By Enzymes That Generate Carbanionic Intermediates: Implications For Ros Production, Cancer Etiology, And Neurodegenerative Diseases, Victoria Bunik, John Schloss, John T. Pinto, Natalia Dudareva, Arthur J L Cooper

NYMC Faculty Publications

Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental …