DTI of Developmental and Pediatric Disorders
Andrei I. Holodny in Functional Neuroimaging, 2019
The central nervous system (CNS) undergoes profound and predictable developmental changes during the first few years of life that provide the structural and functional elements necessary for normal neurological development. The establishment and maturation of white matter pathways, which are heavily dependent on the process of myelination, are critical components of the developing nervous system. Myelin, which is produced by oligodendrocytes, is the phospholipid layer that surrounds axons and increases the impulse propagation speed by saltatory conduction. Myelination, which begins around the fourth month of gestation, predominantly occurs during the first few years of life and continues into early adulthood. Dysmyelination (failure of formation of normal myelin) and demyelination (destruction of myelin) are the common denominators in childhood leukodystrophies. In these disorders, the failure of myelination produces deficits in motor and cognitive function because of impairment of white matter pathways that link various gray matter regions.
Local Anesthetics and Additives
Bernard J. Dalens, Jean-Pierre Monnet, Yves Harmand in Pediatric Regional Anesthesia, 2019
This all-or-none mechanism of conduction at the surface of the axonal membrane is operative in unmyelinated (C) fibers, whereas it is markedly modified by the presence of myelin, which plays the role of an insulating sheath. At the nodes of Ranvier, the axonal membrane is enriched in sodium channels and thus is markedly more excitable than the rest of the cell membrane. Since it also directly contacts the extracellular fluid at this level, depolarizing impulses can “jump” from node to node. This saltatory conduction considerably speeds the transmission of impulses in myelinated fibers. Since the (regular) intervals between adjacent nodes of Ranvier increase with the thickness of both the nerve fiber and the myelin sheath, the conduction speed increases with the size of the nerve fibers, from unmyelinated C fibers to large myelinated Aα fibers Figure 3.5 and Table 3.4).
Clinical Neurophysiology
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
Factors that may affect the amplitude of the CMAP and the motor conduction velocity are shown in Table 5.2. It is worth noting that ‘normal’ conduction velocities are based on the measurements of the fastest conducting large diameter fibres, and loss of these fibres as part of a general loss of axons may lead to slowing of the measured conduction velocity. In addition, in regenerating axons, the nodes of Ranvier are more closely spaced; saltatory conduction is therefore slower. Thus slowing of motor conduction is not limited to demyelinating lesions (demyelinating neuropathies) and can occur in conditions primarily affecting axons (axonal neuropathies). Interpretation depends on the clinical scenario and timing of the study in relation to the nerve damage.
Remyelination therapies for multiple sclerosis: optimizing translation from animal models into clinical trials
Published in Expert Opinion on Investigational Drugs, 2021
Rujapope Sutiwisesak, Terry C. Burns, Moses Rodriguez, Arthur E. Warrington
The pathology of MS is characterized by areas of progressive demyelination or ‘plaques’ at multiple sites within the CNS [6]. Although demyelination is the main pathology, MS lesions occur in both white and gray matter. A healthy myelin sheath, formed by oligodendrocytes in the CNS, enables efficient nerve impulse transmission by utilizing saltatory conduction and maintaining axonal health [7]. Damage to myelin sheaths results in axonal conduction block in the early stages of disease. Axonal damage is usually acute and reversible but axonal loss and dysfunction are the causes of permanent neurological deficits. Progressive neurodegeneration can result from untreated or chronic disease progression. As such, a central goal of MS treatments is axonal preservation, which could be achievable by preventing ongoing damage to myelin sheaths and promoting remyelination.
Gene therapy for neurological disorders: challenges and recent advancements
Published in Journal of Drug Targeting, 2020
Stefanie A. Pena, Rahul Iyengar, Rebecca S. Eshraghi, Nicole Bencie, Jeenu Mittal, Abdulrahman Aljohani, Rahul Mittal, Adrien A. Eshraghi
The brain has a complex and heterogeneous structure, yet neurons have remained the most investigated central nervous system (CNS) cell type [6]. However, with recent biomedical advancements the roles of other cell subpopulations within the brain are proving to be intricately associated with the pathogenesis of many neurological disorders (Figure 2). Microglia comprises 10–15% of the total brain cells and is the resident immune cells of the CNS that perform normal brain surveillance [26]. Oligodendrocytes are responsible for myelination of axons in the CNS, and electrically insulate the axons providing the ability for rapid nerve conduction through saltatory conduction [27]. Astrocytes are the principle glial cells and are the most abundant cell type in the brain. These glial cells play a critical role in the structural component that encompasses the tight junctions of the blood–brain barrier (BBB) [28] (Figure 2). Neurological diseases have unique pathogenesis, which requires gene therapy delivery modalities that can target specific cell subpopulations. To administer these targeted gene delivery, various routes such as parenchymal injections have been employed. The major challenge that still remains to be addressed is to obtain global gene expression in the brain [29].
Ultrastructural and morphometric alterations to the peripheral nerve following the administration of immunosuppressive agent tacrolimus (FK506)
Published in Ultrastructural Pathology, 2021
Ferda Topal Celikkan, Nazli Hayirli Ozyol, Hilal Nakkas, Oya Evirgen
G-ratio, which is frequently used as a structural and functional indicator of optimal axonal myelination, is an important parameter for the exploration of the myelinated nerve fibers during the evaluation of damage and regeneration processes. In peripheral nerves, G-ratio of myelinated axons, which is considered normal in the range between 0.60 and 0.80, is optimal for the saltatory conduction speed of nerve impulses.20–23 We found that G-ratio of control and experimental groups were in normal range and there was no statistically significant difference between the groups. This indicates that despite the presence of statistically significant increase in fiber diameter, axonal diameter, and myelin thickness in 2-week tacrolimus-treated group, still myelinated fibers have optimal myelination in order to facilitate nerve impulse conduction.
Related Knowledge Centers
- Action Potential
- Axon
- Nerve Conduction Velocity
- Node of Ranvier
- Ventral Nerve Cord
- Myelin
- Neuroscience
- Node of Ranvier
- Neuron
- Ion Transporter
- Bioelectrochemistry