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Articles 31 - 47 of 47
Full-Text Articles in Neurology
Recent Advances In Our Molecular And Mechanistic Understanding Of Misfolded Cellular Proteins In Alzheimer’S Disease (Ad) And Prion Disease (Prd), Walter J. Lukiw
Recent Advances In Our Molecular And Mechanistic Understanding Of Misfolded Cellular Proteins In Alzheimer’S Disease (Ad) And Prion Disease (Prd), Walter J. Lukiw
School of Medicine Faculty Publications
Naturally occurring neuron-abundant proteins including amyloid Aβ42 peptide and the microtubule-associated protein tau (MAPT) can, over time and under pathological situations, assume atypical conformations, altering their normal biological structure and function, and causing them to aggregate into insoluble and neurotoxic intracellular inclusions. These misfolded proteins ultimately contribute to the pathogenesis of several progressive, age-related and ultimately lethal human neurodegenerative disorders. The molecular mechanism of this pathological phenomenon of neuronal protein misfolding lends support to the ‘prion hypothesis’, which predicts that the aberrant folding of endogenous natural protein structures into unusual pathogenic isoforms can induce the atypical folding of other similar …
New Inroads Into Our Understanding Of The Tauopathies, Alzheimer's Disease, And The Contribution Of Altered Protein Conformation To Human Neurological Disease, Walter J. Lukiw
School of Medicine Faculty Publications
No abstract provided.
Down-Regulation Of Cyclin D2 In Amyloid Β Toxicity, Inflammation, And Alzheimer’S Disease, Joanna B. Strosznajder, Grzegorz A. Czapski, Magdalena Cieślik, Emilia Białopiotrowicz, Walter J. Lukiw
Down-Regulation Of Cyclin D2 In Amyloid Β Toxicity, Inflammation, And Alzheimer’S Disease, Joanna B. Strosznajder, Grzegorz A. Czapski, Magdalena Cieślik, Emilia Białopiotrowicz, Walter J. Lukiw
School of Medicine Faculty Publications
In the current study, we analyzed the effects of the systemic inflammatory response (SIR) and amyloid β (Aβ) peptide on the expression of genes encoding cyclins and cyclin-dependent kinase (Cdk) in: (i) PC12 cells overexpressing human beta amyloid precursor protein (βAPP), wild-type (APPwt-PC12), or carrying the Swedish mutantion (APPsw-PC12); (ii) the murine hippocampus during SIR; and (iii) Alzheimer’s disease (AD) brain. In APPwtPC12 expression of cyclin D2 (cD2) was exclusively reduced, and in APPsw-PC12 cyclins cD2 and also cA1 were down-regulated, but cA2, cB1, cB2, and cE1 were up-regulated. In the SIR cD2, cB2, cE1 were found to be significantly …
Muscle Selection And Dosing In A Phase 3, Pivotal Study Of Abobotulinumtoxina Injection In Upper Limb Muscles In Children With Cerebral Palsy, Joyce Oleszek, Ann Tilton, Jorge Carranza Del Rio, Nigar Dursun, Marcin Bonikowski, Edward Dabrowski, Simon Page, Benjamin Regnault, Catherine Thompson, Mauricio R. Delgado
Muscle Selection And Dosing In A Phase 3, Pivotal Study Of Abobotulinumtoxina Injection In Upper Limb Muscles In Children With Cerebral Palsy, Joyce Oleszek, Ann Tilton, Jorge Carranza Del Rio, Nigar Dursun, Marcin Bonikowski, Edward Dabrowski, Simon Page, Benjamin Regnault, Catherine Thompson, Mauricio R. Delgado
School of Medicine Faculty Publications
Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle …
Combined Therapy With Avastin, A Paf Receptor Antagonist And A Lipid Mediator Inhibited Glioblastoma Tumor Growth, Valerie A. Cruz Flores, Hemant Menghani, Pranab K. Mukherjee, Luis Marrero, Andre Obenaus, Quan Dang, Larissa Khoutorova, Madigan M. Reid, Ludmila Belayev, Nicolas G. Bazan
Combined Therapy With Avastin, A Paf Receptor Antagonist And A Lipid Mediator Inhibited Glioblastoma Tumor Growth, Valerie A. Cruz Flores, Hemant Menghani, Pranab K. Mukherjee, Luis Marrero, Andre Obenaus, Quan Dang, Larissa Khoutorova, Madigan M. Reid, Ludmila Belayev, Nicolas G. Bazan
School of Medicine Faculty Publications
Glioblastoma multiforme (GBM) is an aggressive, highly proliferative, invasive brain tumor with a poor prognosis and low survival rate. The current standard of care for GBM is chemotherapy combined with radiation following surgical intervention, altogether with limited efficacy, since survival averages 18 months. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the dysregulation of numerous signaling pathways. Recently emerging therapies to precisely modulate tumor angiogenesis, inflammation, and oxidative stress are gaining attention as potential options to combat GBM. Using a mouse model of GBM, this study aims to investigate Avastin (suppressor of vascular endothelial …
Rupture Of A Superficial Temporal Artery Pseudoaneurysm Following Craniotomy, Jessica A. Shields, Jared M. Robichaux, Kevin Morrow, Clifford Crutcher, Gabriel Tender
Rupture Of A Superficial Temporal Artery Pseudoaneurysm Following Craniotomy, Jessica A. Shields, Jared M. Robichaux, Kevin Morrow, Clifford Crutcher, Gabriel Tender
School of Medicine Faculty Publications
Pseudoaneurysm of the superficial temporal artery (STA) is a rare entity that has been reported in the literature after trauma or iatrogenic injuries. We describe a unique case of STA pseudoaneurysm rupture and the clinical sequelae associated with its rupture. We report a case of pseudoaneurysm rupture of the STA that occurred 14 days after craniotomy for cerebrospinal fluid leak repair. We also review the literature, diagnosis and treatment of external carotid artery aneurysms. Rupture of a STA pseudoaneurysm is a previously unreported and serious complication that must be quickly recognized in order to control hemorrhage that may have life …
Microrna-146a-5p, Neurotropic Viral Infection And Prion Disease (Prd), Aileen I. Pogue, Walter J. Lukiw
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 …
Regulation Of Microrna Expression In Sleep Disorders In Patients With Epilepsy, Edyta Dziadkowiak, Justyna Chojdak-Łukasiewicz, Piotr Olejniczak, Bogusław Paradowski
Regulation Of Microrna Expression In Sleep Disorders In Patients With Epilepsy, Edyta Dziadkowiak, Justyna Chojdak-Łukasiewicz, Piotr Olejniczak, Bogusław Paradowski
School of Medicine Faculty Publications
The effects of epilepsy on sleep and the activating effects of sleep on seizures are well documented in the literature. To date, many sleep-related and awake-associated epilepsy syndromes have been described. The relationship between sleep and epilepsy has led to the recognition of polysomnographic testing as an important diagnostic tool in the diagnosis of epilepsy. The authors analyzed the available medical database in search of other markers that assess correlations between epilepsy and sleep. Studies pointing to microRNAs, whose abnormal expression may be common to epilepsy and sleep disorders, are promising. In recent years, the role of microRNAs in the …
Emergency Use Of Targeted Osmotic Lysis For The Treatment Of A Patient With Aggressive Late-Stage Squamous Cell Carcinoma Of The Cervix, Harry J. Gould, Paige R. Miller, Samantha Edenfield, Kelly Jean Sherman, Chad K. Brady, Dennis Paul
Emergency Use Of Targeted Osmotic Lysis For The Treatment Of A Patient With Aggressive Late-Stage Squamous Cell Carcinoma Of The Cervix, Harry J. Gould, Paige R. Miller, Samantha Edenfield, Kelly Jean Sherman, Chad K. Brady, Dennis Paul
School of Medicine Faculty Publications
Upregulation of voltage-gated sodium channels (VGSCs) and Na+/K+-ATPase (sodium pumps) is common across most malignant carcinomas. Targeted osmotic lysis (TOL) is a developing technology in which the concomitant stimulation of VGSCs and pharmacological blockade of sodium pumps causes rapid selective osmotic lysis of carcinoma cells. This treatment of cervical carcinoma is evidence that TOL is a safe, well-tolerated and effective treatment for aggressive advanced carcinomas that has the potential to extend life without compromising its quality. TOL is likely to have broad application for the treatment of advanced-stage carcinomas.
Neurological Complications Of Covid19 During March 2020 At Lcmc Health University Medical Center: Dataset, David Chachkhiani, Michael Y. Soliman, Delphi Barua, Marine Isakadze, Nicole R. Villemarette-Pittman, Deidre J. Devier, Jesus F. Lovera
Neurological Complications Of Covid19 During March 2020 At Lcmc Health University Medical Center: Dataset, David Chachkhiani, Michael Y. Soliman, Delphi Barua, Marine Isakadze, Nicole R. Villemarette-Pittman, Deidre J. Devier, Jesus F. Lovera
School of Medicine Faculty Publications
We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint …
Efficacy And Safety Of Abobotulinumtoxina For Upper Limb Spasticity In Children With Cerebral Palsy: A Randomized Repeat-Treatment Study, Mauricio R. Delgado, Ann Tilton, Jorge Carranzo-Del Rio, Nigar Dursun, Marcin Bonikowski, Resa Aydin, Iwona Maciag-Tymecka, Joyce Oleszek, Edward Dabrowski, Anne-Sophie Grandoulier, Philippe Picaut, The Dysport In Pul Study Group
Efficacy And Safety Of Abobotulinumtoxina For Upper Limb Spasticity In Children With Cerebral Palsy: A Randomized Repeat-Treatment Study, Mauricio R. Delgado, Ann Tilton, Jorge Carranzo-Del Rio, Nigar Dursun, Marcin Bonikowski, Resa Aydin, Iwona Maciag-Tymecka, Joyce Oleszek, Edward Dabrowski, Anne-Sophie Grandoulier, Philippe Picaut, The Dysport In Pul Study Group
School of Medicine Faculty Publications
Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2–17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], …
Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw
Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw
School of Medicine Faculty Publications
Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …
Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder
Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder
School of Medicine Faculty Publications
Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 …
Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan
Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan
School of Medicine Faculty Publications
Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods: We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; …
Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
School of Medicine Faculty Publications
The high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury. RvD6si applied to the eye surface elicits a specific transcriptome signature in the trigeminal ganglion (TG) that includes Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas genes related …
Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo
Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo
School of Medicine Faculty Publications
The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …
Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya
Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya
School of Medicine Faculty Publications
Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic …