Search results for "Sclerosis"

Possible Pathomechanisms Responsible for Injury to the Central Nervous System in the Settings of Chronic Cerebrospinal Venous Insufficiency

2012

The discovery of stenoses in the azygous and internal jugular veins, the so-called chronic cerebrospinal venous insufficiency that accompanies multiple sclerosis, has enabled the reinterpretation of knowledge about this neurologic dis- ease. Pathologic venous outflow from the central nervous system appears to lead to two main problems. Firstly, it disas- sembles the blood-brain barrier and may allow the penetration of nervous parenchyma by glutamate and leukocytes. Sec- ondly, it may result in significant hypoperfusion of the brain and spinal cord. These two overlapping pathologies are likely to trigger plaques through caspase-1-driven pyroptosis of oligodendrocytes and to evoke neurodegene…

IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments.

2014

Multiple sclerosis (MS), an autoimmune neurological disorder, is driven by self-reactive T helper (Th) cells. Research on the role of Th17 lymphocytes in MS pathogenesis has made significant progress in identifying various immunological as well as environmental factors that induce the differentiation and expansion of these cells, different subsets of Th17 cells with varying degrees of pathogenicity, and the role of the secreted effector cytokines. While approved therapies for MS offer significant benefit to patients, there remain unmet needs. Ongoing clinical trials aim to translate the advanced knowledge of Th17 cytokines to improved therapies. This review discusses the current status and …

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice

2011

Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtaine…

Rat CNS cell culture. Enhancement of neuronal survival and delay of glial proliferation by serum from patients with multiple sclerosis. A morphologic…

1984

The addition of serum from multiple sclerosis (MS) patients to the culture medium of dissociated cells from cerebral hemispheres of rat embryos caused a delay in glial proliferation and an enhancement of neuronal survival. Sera from normal individuals and patients with other neurological diseases failed to show this effect. These morphological observations are interpreted as the outcome of inhibition of in vitro gliogenesis.

Glutamate Excitotoxicity in the Cerebellum Mediated by IL-1β

2013

Multiple sclerosis (MS) is the prototypic inflammatory demyelinating disorder of the CNS. Symptoms of cerebellar dysfunction, such as tremors and ataxia, are relatively common in MS, but available treatment options are generally of limited value. Although many clinical manifestations of MS are

Mo-P2:199 Indium-111 oxine platelets survival in patients suffering of cardiac and cerebral arteriosclerosis

2006

Reinterpreting the Magnetic Resonance Signs of Hemodynamic Impairment in the Brains of Multiple Sclerosis Patients From the Perspective of a Recent D…

2010

Multiple sclerosis patients examined with perfusion magnetic resonance (MR) imaging techniques have been found to have patterns of abnormal blood flow. These include prolonged mean transit time, a trend toward decreased cerebral blood flow in the area of plaques, and decreased cerebral blood flow and prolonged mean transit time within normal-appearing white matter. In-creased cerebral blood flow and volume and decreased mean transit time (compared with the baseline values before the relapse) were found to precede the development of plaques. In addition, susceptibility-weighted imaging utilizing deoxyhemoglobin as the contrast has revealed that venous blood in cerebral veins of multiple scle…

Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and aggregation

2021

AbstractPost-translational modifications (PTMs) have emerged as key modulators of protein phase separation and have been linked to protein aggregation in neurodegenerative disorders. The major aggregating protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the RNA-binding protein TDP-43, is hyperphosphorylated in disease on several C-terminal serine residues, which is generally believed to promote TDP-43 aggregation. Here, we show that hyperphosphorylation by Casein kinase 1δ or C-terminal phosphomimetic mutations surprisingly reduce TDP-43 phase separation and aggregation and render TDP-43 condensates more liquid-like and dynamic. Multi-scale simulations revea…

The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.

2019

Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sus…

Atherosclerosis as an inflammatory disease.

2011

In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell type-specific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vasc…