scholarly journals Effects of CNS Demyelination and Myelin Recovery on Urinary Physiology

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 119-120
Author(s):  
Ramalakshmi Ramasamy ◽  
Dawn Rosenberg ◽  
Cara Hardy ◽  
Stephen Crocker ◽  
Phillip Smith
Keyword(s):  
Demyelinating Disease ◽  
Urinary Dysfunction ◽  
Urinary Function ◽  
Volume Sensitivity ◽  
Cns Neurons ◽  
Molecular Studies ◽  
The Central Nervous System ◽  
Cns Demyelination ◽  
The Impact ◽  
Treatment Pressure

Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of note, over 80% of MS patients have urinary symptoms as one of their earliest symptoms. Since MS patients often live into older age, urinary incontinence and retention are significant problems for which few if any effective preventive or therapeutic options are available. The mechanisms by which MS contributes to urinary dysfunction are not well understood. We propose to elucidate the impact of demyelination on urinary performance using the cuprizone model, a model used to study the effects of CNS demyelination and spontaneous remyelination. We hypothesize that CNS demyelination in the cuprizone model will result in aberrant changes in urinary function, and that after remyelination occurs this dysfunction will be alleviated. C57Bl/6 mice were treated with cuprizone (0.2% w/w) for four weeks to induce demyelination. One group was allowed four additional weeks to recover from demyelination, while the other continued cuprizone treatment. Following this eight-week treatment, pressure/flow cystometry, electromyography, and molecular studies were performed to assess demyelination-induced differences in urinary performance. Cuprizone-recovery mice displayed improvements in cystometric function compared to their demyelinated littermates, as seen through improved volume sensitivity and voiding efficiency. Pharmacologic studies showed no significant changes in contractile responsiveness. Thus, we conclude that CNS demyelination results in aging-like phenotype and urinary dysfunction consistent with that observed in clinical disease. Therapeutics aimed at increasing the remyelination potential of the CNS neurons offer the possibility of alleviating urinary dysfunction associated with MS.

scholarly journals Insight and Resources From a Study of the “Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology

2019 ◽  
Vol 47 (8) ◽  
pp. 1038-1042 ◽  
Author(s):  
Hannah Ruetten ◽  
Kyle A. Wegner ◽  
Helen L. Zhang ◽  
Peiqing Wang ◽  
Jaskiran Sandhu ◽  
...  
Keyword(s):  
North Carolina ◽  
Quantitative Methods ◽  
Urinary Dysfunction ◽  
Aging Male ◽  
Urinary Function ◽  
Annual Symposium ◽  
Mouse Prostate ◽  
Prostate Size ◽  
The Impact ◽  
Comparative Histology

The purpose of this symposium report is to summarize information from a session 3 oral presentation at the Society of Toxicologic Pathology Annual Symposium in Raleigh, North Carolina. Mice are genetically tractable and are likely to play an important role in elucidating environmental, genetic, and aging-related mechanisms of urinary dysfunction in men. We and others have made significant strides in developing quantitative methods for assessing mouse urinary function and our collaborators recently showed that aging male mice, like men, develop urinary dysfunction. Yet, it remains unclear how mouse prostate anatomy and histology relate to urinary function. The purpose of this report is to share foundational resources for evaluating mouse prostate histology and urinary physiology from our recent publication “Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology: Functional Assessment.” We will begin with a review of prostatic embryology in men and mice, then move to comparative histology resources, and conclude with quantitative measures of rodent urinary physiology.

scholarly journals The Impact of Multiple Sclerosis Disease Status and Subtype on Hematological Profile

2021 ◽  
Vol 18 (6) ◽  
pp. 3318
Author(s):  
Jacob M. Miller ◽  
Jeremy T. Beales ◽  
Matthew D. Montierth ◽  
Farren B. Briggs ◽  
Scott F. Frodsham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Random Forest ◽  
Demyelinating Disease ◽  
Complete Blood Count ◽  
Disease Status ◽  
Multiple Sclerosis Disease ◽  
Forest Models ◽  
Random Forest Models ◽  
The Central Nervous System ◽  
The Impact

Multiple sclerosis (MS) is an immune-mediated, demyelinating disease of the central nervous system. In this study, an MS cohort and healthy controls were stratified into Caucasian and African American groups. Patient hematological profiles—composed of complete blood count (CBC) and complete metabolic panel (CMP) test values—were analyzed to identify differences between MS cases and controls and between patients with different MS subtypes. Additionally, random forest models were used to determine the aggregate utility of common hematological tests in determining MS disease status and subtype. The most significant and relevant results were increased bilirubin and creatinine in MS cases. The random forest models achieved some success in differentiating between MS cases and controls (AUC values: 0.725 and 0.710, respectively) but were not successful in differentiating between subtypes. However, larger samples that adjust for possible confounding variables, such as treatment status, may reveal the value of these tests in differentiating between MS subtypes.

scholarly journals JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

2007 ◽  
Vol 82 (3) ◽  
pp. 1558-1569 ◽  
Author(s):  
Nana Merabova ◽  
Dorota Kaniowska ◽  
Rafal Kaminski ◽  
Satish L. Deshmane ◽  
Martyn K. White ◽  
...  
Keyword(s):  
Demyelinating Disease ◽  
Jc Virus ◽  
Regulatory Protein ◽  
T Antigen ◽  
Productive Infection ◽  
Oligodendrocyte Differentiation ◽  
Virus Life Cycle ◽  
The Central Nervous System ◽  
The Impact

ABSTRACT Productive infection of oligodendrocytes, which are responsible for the formation of myelin sheath in the central nervous system, with the human neurotropic virus JC virus (JCV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition to encoding T antigen and the capsid proteins, which are produced at the early and late phases of the infection cycle, respectively, JCV encodes a small regulatory protein named agnoprotein that is important for successful completion of the virus life cycle. Here we used bipotential CG-4 cells to examine the impact of agnoprotein on oligodendrocyte differentiation and survival in the absence of JCV lytic infection. We demonstrate that the expression of agnoprotein delayed the formation of complex outgrowth networks of the cells during oligodendrocyte differentiation. These alterations were accompanied by high levels of DNA damage, induction of proapoptotic proteins, and suppression of prosurvival signaling. Accordingly, apoptosis was significantly increased upon the induction of CG-4 cells toward differentiation in cells expressing agnoprotein. These observations provide the first evidence for the possible involvement of agnoprotein, independent from its role in viral replication, in a series of biological events that may contribute to the pathological features seen in PML lesions.

scholarly journals Effects of aquatic exercises in a rat model of brainstem demyelination with ethidium bromide on the beam walking test

2009 ◽  
Vol 67 (3a) ◽  
pp. 652-656 ◽  
Author(s):  
Cíntia Cristina Souza Nassar ◽  
Eduardo Fernandes Bondan ◽  
Sandra Regina Alouche
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Experimental Model ◽  
Ethidium Bromide ◽  
Motor Performance ◽  
Demyelinating Disease ◽  
Control Group ◽  
Walking Test ◽  
The Central Nervous System ◽  
The Impact

Multiple sclerosis is a demyelinating disease of the central nervous system associated with varied levels of disability. The impact of early physiotherapeutic interventions in the disease progression is unknown. We used an experimental model of demyelination with the gliotoxic agent ethidium bromide and early aquatic exercises to evaluate the motor performance of the animals. We quantified the number of footsteps and errors during the beam walking test. The demyelinated animals walked fewer steps with a greater number of errors than the control group. The demyelinated animals that performed aquatic exercises presented a better motor performance than those that did not exercise. Therefore aquatic exercising was beneficial to the motor performance of rats in this experimental model of demyelination.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Acute Disseminated Encephalomyelitis (ADEM): A Demyelinating Disease with Specific Morphological Features

2021 ◽  
pp. 106689692199356
Author(s):  
Fleur Cordier ◽  
Lars Velthof ◽  
David Creytens ◽  
Jo Van Dorpe
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Differential Diagnosis ◽  
Clinical Case ◽  
Demyelinating Disease ◽  
Acute Disseminated Encephalomyelitis ◽  
Demyelinating Diseases ◽  
Demyelinating Disorder ◽  
Immune Mediated ◽  
The Central Nervous System

Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory and demyelinating disorder of the central nervous system. Its characteristic perivenular demyelination and inflammation aid in the differential diagnosis with other inflammatory demyelinating diseases. Here, we present a clinical case of ADEM, summarize its histological hallmarks, and discuss pitfalls concerning the most important neuropathological differential diagnoses.

scholarly journals Biology of the repair of central nervous system demyelinated lesions: an appraisal

1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Demyelinating Disease ◽  
Experimental Models ◽  
Primitive Cell ◽  
Marked Influence ◽  
Myelin Sheaths ◽  
Human Material ◽  
The Central Nervous System

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Paulo Roberto Arruda Zantut ◽  
Mariana Matera Veras ◽  
Sarah Gomes Menezes Benevenutto ◽  
Angélica Mendonça Vaz Safatle ◽  
Ricardo Augusto Pecora ◽  
...  
Keyword(s):  
Young Adult ◽  
Light Microscopy ◽  
Prenatal Exposure ◽  
Structural Changes ◽  
Volume Fraction ◽  
Clinical Care ◽  
Retinal Layer ◽  
Exposed Population ◽  
The Central Nervous System ◽  
The Impact

Abstract Background Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.

scholarly journals Mutations That Affect the Tropism of DA and GDVII Strains of Theiler's Virus In Vitro Influence Sialic Acid Binding and Pathogenicity

2002 ◽  
Vol 76 (16) ◽  
pp. 8138-8147 ◽  
Author(s):  
Karima Jnaoui ◽  
Muriel Minet ◽  
Thomas Michiels
Keyword(s):  
Sialic Acid ◽  
Demyelinating Disease ◽  
Binding Capacity ◽  
Single Amino Acid ◽  
Sialic Acid Binding ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Different Strains ◽  
Single Amino Acid Mutation

ABSTRACT Theiler's murine encephalomyelitis virus (TMEV) is a natural pathogen of the mouse. The different strains of TMEV are divided into two subgroups according to the pathology they provoke. The neurovirulent strains GDVII and FA induce an acute fatal encephalitis, while persistent strains, like DA and BeAn, cause a chronic demyelinating disease associated with viral persistence in the central nervous system. Different receptor usage was proposed to account for most of the phenotype difference between neurovirulent and persistent strains. Persistent but not neurovirulent strains were shown to bind sialic acid. We characterized DA and GDVII derivatives adapted to grow on CHO-K1 cells. Expression of glycosaminoglycans did not influence infection of CHO-K1 cells by parental and adapted viruses. Mutations resulting from adaptation of DA and GDVII to CHO-K1 cells notably mapped to the well-characterized VP1 CD and VP2 EF loops of the capsid. Adaptation of the DA virus to CHO-K1 cells correlated with decreased sialic acid usage for entry. In contrast, adaptation of the GDVII virus to CHO-K1 cells correlated with the appearance of a weak sialic acid usage for entry. The sialic acid binding capacity of the GDVII variant resulted from a single amino acid mutation (VP1-51, Asn→Ser) located out of the sialic acid binding region defined for virus DA. Mutations affecting tropism in vitro and sialic acid binding dramatically affected the persistence and neurovirulence of the viruses.

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