scholarly journals Multiple Sclerosis: LIFNano-CD4 for Trojan Horse Delivery of the Neuro-Protective Biologic “LIF” Into the Brain: Preclinical Proof of Concept

2021 ◽  
Vol 3 ◽  
Author(s):  
Raul de la Flor ◽  
Janette Robertson ◽  
Rostislav V. Shevchenko ◽  
Mo Alavijeh ◽  
Sean Bickerton ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Self Tolerance ◽  
Current Therapies ◽  
Cognate Antigen ◽  
The Central Nervous System ◽  
Therapeutic Properties ◽  
Nano Formulation ◽  
The Brain ◽  
Treg Phenotype ◽  
Stem Cell Growth Factor

Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest late twenties. There is no cure, and current therapies are immunosuppressive only. LIF is a vital stem cell growth factor active throughout life—and essential for health of the central nervous system (CNS), being tolerogenic, myelinogenic, and neuroprotective. Nano-formulation of LIF (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic properties, increasing potency 1,000-fold when targeted to CD4 (LIFNano-CD4). Moreover, circulating CD4+ lymphocytes are themselves regulated by LIF to express the Treg phenotype, known to release T cell-derived LIF upon engagement with cognate antigen, perpetuating antigen-specific self-tolerance. With the longer-term aim of treating inflammatory lesions of MS, we asked, does LIFNano-CD4 cross the blood–brain barrier (BBB)? We measure pK and pD using novel methodologies, demonstrate crossing of the BBB, show LIF-cargo-specific anti-inflammatory efficacy in the frontal cortex of the brain, and show safety of intravenous delivery of LIFNano-CD4 at doses known to provide efficacious concentrations of LIF cargo behind the BBB.

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

2021 ◽  
pp. 109980042110500
Author(s):  
Pamela Newland ◽  
Yelyzaveta Basan ◽  
Ling Chen ◽  
Gregory Wu
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Markers ◽  
Pearson Correlation ◽  
Correlation Coefficients ◽  
The United States ◽  
Biological Mechanisms ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p = .024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS.

scholarly journals PECULIARITIES OF THE CLINICAL COURSE OF POSTMEASLES ENCEPHALITIS IN IMMUNOSUPRESSED PEOPLE

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Tetiana Nehrych ◽  
◽  
Maria Shorobura ◽  
Irina Hritsyna ◽  
Liliia Yukhimiv ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Inclusion Body ◽  
Bacterial Pneumonia ◽  
Clinical Course ◽  
Risk Group ◽  
Neurological Complications ◽  
Immunosuppressive Drugs ◽  
The Central Nervous System ◽  
The Brain

Primary acute measles encephalitis and acute postmeasles encephalitis are the most common neurological complications of measles. It is important to detect encephalitis, which develops a month or more after the manifestations of measles infection. These encephalitis are rare and occur mainly in people with immunodefi ciency. Multiple sclerosis is a chronic disease of the central nervous system for the treatment of which diseasemodifying therapy is used, namely monoclonal antibodies, that can lead to immunosuppression and immunodefi ciency. Nowadays, there is insuffi cient information about the course of postcortical encephalitis in patients with multiple sclerosis who are taking immunosuppressive drugs. The article presents data on the clinical classifi cation, diagnosis and treatment of measles encephalitis. A clinical case of measles inclusion body encephalitis in a thirty-threeyear-old patient with multiple sclerosis on the background of annual intake of monoclonal antibodies is presented. She also had viral-bacterial pneumonia and developed disseminated intravascular coagulation in the brain and lungs. These complications of measles infection led to the death of the person after a month and a half of intensive care. Thus, patients with multiple sclerosis who are taking drugs with immunosuppressive eff ects are among the risk group for measles inclusion body encephalitis. Measles inclusion body encephalitis in such patients can be severe, which complicates timely diagnosis, proper treatment and leads to death.

scholarly journals Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Genaro G. Ortiz ◽  
Fermín P. Pacheco-Moisés ◽  
Oscar K. Bitzer-Quintero ◽  
Ana C. Ramírez-Anguiano ◽  
Luis J. Flores-Alvarado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Tissue Injury ◽  
Autoimmune Disorder ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
The Brain ◽  
And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

A COMPUTATIONAL MODEL FOR LESION DYNAMICS IN MULTIPLE SCLEROSIS OF THE BRAIN

2008 ◽  
Vol 17 (05) ◽  
pp. 930-939 ◽  
Author(s):  
T. R. KRISHNA MOHAN ◽  
SURAJIT SEN ◽  
MURALI RAMANATHAN
Keyword(s):  
Multiple Sclerosis ◽  
Network Model ◽  
Initial Conditions ◽  
Cell Damage ◽  
Inflammatory Cells ◽  
Pathological Process ◽  
Spatial Spread ◽  
Programmed Death ◽  
The Central Nervous System ◽  
The Brain

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) that is characterized by lesions with inflammatory cells, axons with the insulating myelin sheath damaged, and axonal loss. The causes of MS are not known and there is as yet no cure. The purpose of this research was to evaluate a physically motivated network model for lesion formation in the brain. The parsimonious network model contained two elements: (i) a spatially spreading pathological process causing cell damage and death leading to neuro-degeneration and, (ii) generation of alarm signals by the damaged cells that lead to activation of programmed death of cells surrounding the lesions in an attempt to contain the spatial spread of the pathologic process. Simulation results with a range of network geometries indicated that the model was capable of describing lesion progression and arrest. The modeling results also demonstrated dynamical complexity with sensitivity to initial conditions.

scholarly journals Multiple Sclerosis

2020 ◽  
Author(s):  
Amirhossein Azari Jafari ◽  
Seyyedmohammadsadeq Mirmoeeni
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Autoimmune Disease ◽  
The Central Nervous System ◽  
Genetic And Environmental Factors ◽  
Chronic Autoimmune Disease ◽  
The Brain

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), caused by genetic and environmental factors. It is characterized by intermittent and recurrent episodes of inflammation that result in the demyelination and subsequent damage of the underlying axons present in the brain, optic nerve and spinal cord [1][2][3].

The role of inflammasomes in multiple sclerosis

2020 ◽  
pp. 135245852093277
Author(s):  
Hanie Yavarpour-Bali ◽  
Maryam Ghasemi-Kasman
Keyword(s):  
Multiple Sclerosis ◽  
Protein Complexes ◽  
Critical Role ◽  
Immunosuppressive Drugs ◽  
Inflammasome Activation ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Current Therapies ◽  
The Central Nervous System ◽  
Inflammatory Autoimmune Disease

Multiple sclerosis (MS) is considered as an inflammatory autoimmune disease of the central nervous system (CNS), with a complex and heterogenic etiology. However, the involvement of inflammation in its pathophysiology is well documented and current therapies for MS are mainly immunosuppressive drugs. Although the available drugs reduce new lesions and relapses, their long-term outcome is not completely satisfactory. Inflammasomes are multimeric protein complexes that play a critical role in the inflammatory process. Several lines of evidence suggest an association between inflammasome activation and MS. In this paper, we have reviewed current studies that demonstrate the involvement of inflammasomes in MS development, in both animal model and MS patients. Furthermore, prior studies about the effect of inflammasome inhibitor drugs on development and progression of MS are discussed.

The Aging Brain

2019 ◽  
pp. 1-23
Author(s):  
Rashi Rajput ◽  
Ramneek Kaur ◽  
Rishika Chadha ◽  
Shalini Mani ◽  
Rachana R. ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Decision Making ◽  
Healthy Aging ◽  
Structural Changes ◽  
Neuronal Loss ◽  
Aging Brain ◽  
Protein Oligomerization ◽  
Pathological Characteristic ◽  
The Central Nervous System ◽  
The Brain

Neurodegeneration is the progressive and gradual dysfunction and loss of axons in the central nervous system. It is the main pathological characteristic of chronic and acute neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The usual aspects of pathogenesis of disease can be abridged with regards to the downstream implications of uncontrollable protein oligomerization and aggregation from postmitotic cells. The brain structure constantly changes in normal aging without any dysfunction accompanying the structural changes in brain. The decline in cognitive capabilities, for example, processing speed, memory, and functions related to decision making are the sign of healthy aging. The reduction in brain volume in healthy aging is possibly related to neuronal loss at some marginal extent. The following chapter discusses the structural and functional alterations in the brain in ageing and neurodegeneration.

Application of Artificial Intelligence in Magnetic Resonance Imaging to reduce Gadolinium accumulation in patients with multiple sclerosis: A Review

2021 ◽  
Vol 1 (4) ◽  
pp. 416-428
Author(s):  
Vijay Anant Athavale ◽  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Artificial Intelligence ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
Mri Scans ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
New Onset

Gadolinium (Gd) is a based contrast agent is used for Magnetic Resonance Imaging (MRI). In India, gadobutrolhas been is approved for MRI of the Central Nervous System (CNS), liver, kidneys, and breast. It has been noted in several studies that the accumulation of gadolinium occurs in different structures in the brain. Patients with Multiple Sclerosis (MS) are regularly followed up with MRI scans and MRI with contrast enhancement is the most common method of distinguishing new-onset pathological changes. Developments in technology and methods in artificial intelligence have shown that there is reason to map out the X-ray technician’s work with examinations and medicines administered to patients may be altered to prevent the accumulation of gadolinium.

scholarly journals C3c intrathecal synthesis evaluation in patients with multiple sclerosis

2007 ◽  
Vol 65 (3b) ◽  
pp. 800-802 ◽  
Author(s):  
Bárbara Padilla-Docal ◽  
Alberto J Dorta-Contreras ◽  
Hermes Fundora-Hernández ◽  
Elena Noris-García ◽  
Raisa Bu-Coifiu-Fanego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Complement System ◽  
Progressive Disease ◽  
Degradation Process ◽  
Intrathecal Synthesis ◽  
Brain White Matter ◽  
The Central Nervous System ◽  
The Moment ◽  
The Complement System ◽  
The Brain

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). OBJECTIVE: To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction. METHOD: Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates. RESULTS: High values over 80% of intrathecal synthesis were obtained except in one of the patients. CONCLUSION: Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

scholarly journals MicroRNAs, Multiple Sclerosis and Depression

2021 ◽  
Vol 22 (15) ◽  
pp. 7802
Author(s):  
Hsiuying Wang
Keyword(s):  
Multiple Sclerosis ◽  
Depressive Disorders ◽  
Nitrosative Stress ◽  
Mirna Regulation ◽  
Oxidative And Nitrosative Stress ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Patients Experience ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects the brain and spinal cord. There are several disease courses in MS including relapsing–remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). Up to 50% of MS patients experience depressive disorders. Major depression (MD) is a serious comorbidity of MS. Many dysfunctions including neuroinflammation, peripheral inflammation, gut dysbiosis, chronic oxidative and nitrosative stress, and neuroendocrine and mitochondrial abnormalities may contribute to the comorbidity between MS and MD. In addition to these actions, medical treatment and microRNA (miRNA) regulation may also be involved in the mechanisms of the comorbidity between MS and MD. In the study, I review many common miRNA biomarkers for both diseases. These common miRNA biomarkers may help further explore the association between MS and MD.

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