No Relation Between Cognitive Impairment, Physical Disability and Serum Biomarkers in a Cohort of Progressive Multiple Sclerosis Patients.

Despite significant efforts, there is still an existing need to identify diagnostic tools that would enable fast and reliable detection of the progressive stage of multiple sclerosis (MS) and help in monitoring the disease course and/or treatment effects. The aim of this prospective study in a group of people with progressive MS was to determine whether changes in the levels of selected serum biomarkers and in cognitive function may predict disease progression, and therefore refine the decision-making process in the evaluation of MS patients. Forty two (42) patients with progressive MS completed all the study procedures; the mean duration of follow-up was 12.

CHI3L1 in Multiple Sclerosis-From Bench to Clinic.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is likely to play a role in the physiological development of the CNS. CHI3L1 is primarily produced by CNS macrophages, microglia, and activated astrocytes.

Predictive value of brain atrophy, serum biomarkers and information processing speed for early disease progression in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement.

Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS).

Methods: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI.

Chemistry and Function of Glycosaminoglycans in the Nervous System.

Proteoglycans, and especially their GAG components, participate in numerous biologically significant interactions with growth factors, chemokines, morphogens, guidance molecules, survival factors, and other extracellular and cell-surface components. These interactions are often critical to the basic developmental processes of cellular proliferation and differentiation, as well as to both the onset of disease sequelae and prevention of disease progression. In many tissues, proteoglycans and especially their glycosaminoglycan (GAG) components are mediators of these processes.

Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development.

The extracellular matrix (ECM) is critically important for most cellular processes including differentiation, morphogenesis, growth, survival and regeneration. The interplay between cells and the ECM often involves bidirectional signaling between ECM components and small molecules, i.e.

Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton's Jelly Mesenchymal Stem Cells Secretome.

Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton's jelly (WJ-MSCs) make them an interesting research and therapeutic model.

Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression.

Background: Neuronal ceroid lipofuscinoses, (NCLs or Batten disease) are a group of inherited, early onset, fatal neurodegenerative diseases associated with mutations in 13 genes. All forms of the disease are characterized by lysosomal accumulation of fluorescent storage material, as well as profound neurodegeneration, but the relationship of the various genes' function to a single biological process is not obvious. In this study, we used a well-characterized mouse model of classical late infantile NCL (cLINCL) in which the tripeptidyl peptidase 1 (Tpp1) gene is disrupted by gene targeting, resulting in loss of detectable TPP1 activity and leading to progressive neurological phenotypes including ataxia, increased motor deficiency, and early death.

Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease.

Neonatal AAV9-gene therapy of the lysosomal enzyme galactosylceramidase (GALC) significantly ameliorates central and peripheral neuropathology, prolongs survival, and largely normalizes motor deficits in Twitcher mice. Despite these therapeutic milestones, new observations identified the presence of multiple small focal demyelinating areas in the brain after 6-8 months. These lesions are in stark contrast to the diffuse, global demyelination that affects the brain of naive Twitcher mice.

Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth.

The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC).

The Role of in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone.

Osteoarthritis and osteoporosis are widely prevalent and have far-reaching public health implications. There is increasing evidence that epigenetics, in particular, histone 3 lysine 79 methyltransferase , plays an important role in the cartilage and bone biology. In this study, we evaluated the role of in the articular cartilage, growth plate, and trabecular bone utilizing conditional KO mouse models.

Comparisons and Approaches of PREP Programs at Different Stages of Maturity: Challenges, Best Practices and Benefits.

The Postbaccalaureate Research Education Programs (PREP) are designed to provide research training and educational opportunities for recent baccalaureate graduates from targeted groups defined by NIH who would benefit by academic enhancements between the completion of undergraduate studies and admission to a PhD program. These programs offer exposure to the biomedical science community in a way that helps post-undergraduate individuals visualize future careers as well-trained, enthusiastic leaders in biomedical research who represent and will promote diversity in science. Specifically, PREPs provide the preparation and skills required for entrance into, and successful completion of, a PhD program via in-depth exposure to a research setting, which helps to refine the post-undergraduate's research interests, assists in providing a realistic understanding of the end results one can expect from research, and offers a forum for discussion with lab peers and mentors about possible career paths.

Multiple Sclerosis CD49dCD154 As Myelin-Specific Lymphocytes Induced During Remyelination.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) mediated by autoreactive lymphocytes. The role of autoreactive lymphocytes in the CNS demyelination is well described, whereas very little is known about their role in remyelination during MS remission. In this study, we identified a new subpopulation of myelin-specific CD49dCD154 lymphocytes presented in the peripheral blood of MS patients during remission, that proliferated in vitro in response to myelin peptides.

MS CD49dCD154 Lymphocytes Reprogram Oligodendrocytes into Immune Reactive Cells Affecting CNS Regeneration.

The critical aspect in multiple sclerosis (MS) progression involves insufficient regeneration of CNS resulting from deficient myelin synthesis by newly generated oligodendrocytes (OLs). Although many studies have focused on the role of autoreactive lymphocytes in the inflammatory-induced axonal loss, the problem of insufficient remyelination and disease progression is still unsolved. To determine the effect of myelin-specific lymphocytes on OL function in MS patients and in a mouse model of MS, we cultured myelin induced MS CD49dCD154 circulating lymphocytes as well as Experimental Autoimmune Encephalomyelitis (EAE) mouse brain-derived T and memory B cells with maturing oligodendrocyte precursor cells (OPCs).

NK Cell Induced T Cell Anergy Depends on GRAIL Expression.

NK cells (natural killer cells) being a part of the innate immune system have been shown to be involved in immunoregulation of autoimmune diseases. Previously we have shown that HINT1/Hsp70 treatment induced regulatory NK cells ameliorating experimental autoimmune encephalomyelitis (EAE) course and CD4+ T cells proliferation. NK cells were isolated from mice treated with HINT1/Hsp70 and co-cultured with proteolipid protein (PLP)-stimulated CD4+ T cells isolated from EAE mice.

Naturally Occurring Nervonic Acid Ester Improves Myelin Synthesis by Human Oligodendrocytes.

The dysfunction of oligodendrocytes (OLs) is regarded as one of the major causes of inefficient remyelination in multiple sclerosis, resulting gradually in disease progression. Oligodendrocytes are derived from oligodendrocyte progenitor cells (OPCs), which populate the adult central nervous system, but their physiological capability to myelin synthesis is limited. The low intake of essential lipids for sphingomyelin synthesis in the human diet may account for increased demyelination and the reduced efficiency of the remyelination process.

Global Brain Transcriptome Analysis of a Tpp1 Neuronal Ceroid Lipofuscinoses Mouse Model.

In humans, homozygous mutations in the TPP1 gene results in loss of tripeptidyl peptidase 1 (TPP1) enzymatic activity, leading to late infantile neuronal ceroid lipofuscinoses disease. Using a mouse model that targets the Tpp1 gene and recapitulates the pathology and clinical features of the human disease, we analyzed end-stage (4 months) transcriptional changes associated with lack of TPP1 activity. Using RNA sequencing technology, Tpp1 expression changes in the forebrain/midbrain and cerebellum of 4-month-old homozygotes were compared with strain-related controls.

C5a-Preactivated Neutrophils Are Critical for Autoimmune-Induced Astrocyte Dysregulation in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neuroinflammatory disease. In contrast to multiple sclerosis, autoantibodies against aquaporin-4 (AQP4) expressed on astrocytic end-feet have been exclusively detected in sera of NMOSD patients. Several lines of evidence suggested that anti-AQP4 autoantibodies are pathogenic, but the mechanism triggering inflammation, impairment of astrocyte function, and the role of neutrophils presented in NMOSD cerebrospinal fluid remains unknown.

Proteoglycans in brain development and pathogenesis.

Proteoglycans are diverse, complex extracellular/cell surface macromolecules composed of a central core protein with covalently linked glycosaminoglycan (GAG) chains; both of these components contribute to the growing list of important bio-active functions attributed to proteoglycans. Increasingly, attention has been paid to the roles of proteoglycans in nervous tissue development due to their highly regulated spatio/temporal expression patterns, whereby they promote/inhibit neurite outgrowth, participate in specification and maturation of various precursor cell types, and regulate cell behaviors like migration, axonal pathfinding, synaptogenesis and plasticity. These functions emanate from both the environments proteoglycans create around cells by retaining ions and water or serving as scaffolds for cell shaping or motility, and from dynamic interactions that modulate signaling fields for cytokines, growth factors and morphogens, which may bind to either the protein or GAG portions.

Glial cell responses in a murine multifactorial perinatal brain injury model.

The impact of traumatic brain injury during the perinatal period, which coincides with glial cell (astrocyte and oligodendrocyte) maturation was assessed to determine whether a second insult, e.g., increased inflammation due to remote bacterial exposure, exacerbates the initial injury's effects, possibly eliciting longer-term brain damage.

Multiple sclerosis: Presence of serum antibodies to lipids and predominance of cholesterol recognition.

A lot of available data on lipid immunology in multiple sclerosis (MS) have been derived from studies using synthetic lipids, therefore the role of lipids in the immunopathogenesis of MS remains poorly defined. The present study on the lipid response in MS was performed on native lipids from autopsied brain tissue. For this, lipid fractions (n = 9) were prepared from MS (n = 3) and control (n = 2) white matter according to the Folch procedure and were characterized depending on their solubility in chloroform/methanol.

Heat shock protein 70 (Hsp70) interacts with the Notch1 intracellular domain and contributes to the activity of Notch signaling in myelin-reactive CD4 T cells.

Notch receptors (Notch1-4) are involved in the differentiation of CD4 T cells and the development of autoimmunity. Mechanisms regulating Notch signaling in CD4 T cells are not fully elucidated. In this study we investigated potential crosstalk between Notch pathway molecules and heat shock protein 70 (Hsp70), the major intracellular chaperone involved in the protein transport during immune responses and other stress conditions.