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Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
by
Mazarakis, Nicholas D.
, Faisal, A. Aldo
, Howell, Owain W.
, Picon, Carmen
, James, Rachel
, Meng, Joanna
, Tan, Li
, Gallego-Delgado, Patricia
, Umashankar, Swetha
, Reynolds, Richard
, Browne, Eleanor
in
Abnormalities
/ Adult
/ Aged
/ Aged, 80 and over
/ Animal models
/ Animal tissues
/ Autopsy
/ Axons
/ Axons - pathology
/ Biology and Life Sciences
/ Brain
/ Brain - pathology
/ Cytoskeleton
/ Degeneration
/ Demyelination
/ Disruption
/ Electrical Synapses - pathology
/ Electrical Synapses - radiation effects
/ Female
/ Genetic aspects
/ Glycoproteins
/ Human tissues
/ Humans
/ Inflammation
/ Inflammation - pathology
/ Male
/ Mediators
/ Medicine and Health Sciences
/ Membrane proteins
/ Microglia
/ Microglia - pathology
/ Middle Aged
/ Molecular interactions
/ Morphology
/ Multiple sclerosis
/ Multiple Sclerosis - diagnostic imaging
/ Multiple Sclerosis - pathology
/ Myelin
/ Myelin Sheath - pathology
/ Nervous system
/ Neurodegeneration
/ Neuroglia - pathology
/ Neuroimmunomodulation - immunology
/ Neuroimmunomodulation - physiology
/ Nodes of Ranvier
/ Pathology
/ Physiological aspects
/ Precentral gyrus
/ Proteins
/ Ranvier's Nodes - pathology
/ Ranvier's Nodes - physiology
/ Sheaths
/ Substantia alba
/ White Matter - diagnostic imaging
/ White Matter - immunology
/ White Matter - pathology
2020
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Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
by
Mazarakis, Nicholas D.
, Faisal, A. Aldo
, Howell, Owain W.
, Picon, Carmen
, James, Rachel
, Meng, Joanna
, Tan, Li
, Gallego-Delgado, Patricia
, Umashankar, Swetha
, Reynolds, Richard
, Browne, Eleanor
in
Abnormalities
/ Adult
/ Aged
/ Aged, 80 and over
/ Animal models
/ Animal tissues
/ Autopsy
/ Axons
/ Axons - pathology
/ Biology and Life Sciences
/ Brain
/ Brain - pathology
/ Cytoskeleton
/ Degeneration
/ Demyelination
/ Disruption
/ Electrical Synapses - pathology
/ Electrical Synapses - radiation effects
/ Female
/ Genetic aspects
/ Glycoproteins
/ Human tissues
/ Humans
/ Inflammation
/ Inflammation - pathology
/ Male
/ Mediators
/ Medicine and Health Sciences
/ Membrane proteins
/ Microglia
/ Microglia - pathology
/ Middle Aged
/ Molecular interactions
/ Morphology
/ Multiple sclerosis
/ Multiple Sclerosis - diagnostic imaging
/ Multiple Sclerosis - pathology
/ Myelin
/ Myelin Sheath - pathology
/ Nervous system
/ Neurodegeneration
/ Neuroglia - pathology
/ Neuroimmunomodulation - immunology
/ Neuroimmunomodulation - physiology
/ Nodes of Ranvier
/ Pathology
/ Physiological aspects
/ Precentral gyrus
/ Proteins
/ Ranvier's Nodes - pathology
/ Ranvier's Nodes - physiology
/ Sheaths
/ Substantia alba
/ White Matter - diagnostic imaging
/ White Matter - immunology
/ White Matter - pathology
2020
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Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
by
Mazarakis, Nicholas D.
, Faisal, A. Aldo
, Howell, Owain W.
, Picon, Carmen
, James, Rachel
, Meng, Joanna
, Tan, Li
, Gallego-Delgado, Patricia
, Umashankar, Swetha
, Reynolds, Richard
, Browne, Eleanor
in
Abnormalities
/ Adult
/ Aged
/ Aged, 80 and over
/ Animal models
/ Animal tissues
/ Autopsy
/ Axons
/ Axons - pathology
/ Biology and Life Sciences
/ Brain
/ Brain - pathology
/ Cytoskeleton
/ Degeneration
/ Demyelination
/ Disruption
/ Electrical Synapses - pathology
/ Electrical Synapses - radiation effects
/ Female
/ Genetic aspects
/ Glycoproteins
/ Human tissues
/ Humans
/ Inflammation
/ Inflammation - pathology
/ Male
/ Mediators
/ Medicine and Health Sciences
/ Membrane proteins
/ Microglia
/ Microglia - pathology
/ Middle Aged
/ Molecular interactions
/ Morphology
/ Multiple sclerosis
/ Multiple Sclerosis - diagnostic imaging
/ Multiple Sclerosis - pathology
/ Myelin
/ Myelin Sheath - pathology
/ Nervous system
/ Neurodegeneration
/ Neuroglia - pathology
/ Neuroimmunomodulation - immunology
/ Neuroimmunomodulation - physiology
/ Nodes of Ranvier
/ Pathology
/ Physiological aspects
/ Precentral gyrus
/ Proteins
/ Ranvier's Nodes - pathology
/ Ranvier's Nodes - physiology
/ Sheaths
/ Substantia alba
/ White Matter - diagnostic imaging
/ White Matter - immunology
/ White Matter - pathology
2020
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Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
Journal Article
Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
2020
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Overview
Changes to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of multiple sclerosis (MS) brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. These pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the lymphotoxin-α (LTα) and interferon-γ (IFNγ) genes. We show that tumour necrosis factor (TNF), IFNγ, and glutamate can provoke paranodal elongation in cerebellar slice cultures, which could be reversed by an N-methyl-D-aspartate (NMDA) receptor blocker. When these changes were inserted into a computational model to simulate axonal conduction, a rapid decrease in velocity was observed, reaching conduction failure in small diameter axons. We suggest that glial cells activated by pro-inflammatory cytokines can produce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and conduction deficits.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Adult
/ Aged
/ Autopsy
/ Axons
/ Brain
/ Electrical Synapses - pathology
/ Electrical Synapses - radiation effects
/ Female
/ Humans
/ Male
/ Medicine and Health Sciences
/ Multiple Sclerosis - diagnostic imaging
/ Multiple Sclerosis - pathology
/ Myelin
/ Neuroimmunomodulation - immunology
/ Neuroimmunomodulation - physiology
/ Proteins
/ Ranvier's Nodes - physiology
/ Sheaths
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