-
Advances in Experimental Medicine and... 2019Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy, and pathophysiologically classified into acute inflammatory demyelinating... (Review)
Review
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy, and pathophysiologically classified into acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN). The main pathophysiological mechanism is complement-mediated nerve injury caused by antibody-antigen interaction in the peripheral nerves. Antiglycolipid antibodies are most pathogenic factors in the development of GBS, but not found in 40% of patients with GBS. One of the principal target regions in GBS is the node of Ranvier where functional molecules including glycolipids are assembled. Nodal dysfunction induced by the immune response in nodal axolemma, termed "nodopathy," can electrophysiologically show reversible conduction failure, axonal degeneration, or segmental demyelination. To detect new target molecules in antiglycolipid antibody-negative GBS and to elucidate the pathophysiology in the subacute and the subsequent phases of the disorder are the next problems.
Topics: Antibodies; Axons; Complement System Proteins; Glycolipids; Guillain-Barre Syndrome; Humans; Neural Conduction; Peripheral Nerves; Ranvier's Nodes
PubMed: 31760653
DOI: 10.1007/978-981-32-9636-7_20 -
International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
Cellular & Molecular Immunology Jun 2018Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to... (Review)
Review
Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.
Topics: Communicable Diseases; Guillain-Barre Syndrome; Humans; Immunity; Myelitis, Transverse
PubMed: 29375121
DOI: 10.1038/cmi.2017.142 -
Frontiers in Neurology 2020Traumatic brain injuries are a leading cause of morbidity and mortality worldwide. With almost 50% of traumatic brain injuries being related to axonal damage,...
Traumatic brain injuries are a leading cause of morbidity and mortality worldwide. With almost 50% of traumatic brain injuries being related to axonal damage, understanding the nature of cellular level impairment is crucial. Experimental observations have so far led to the formulation of conflicting theories regarding the cellular primary injury mechanism. Disruption of the axolemma, or alternatively cytoskeletal damage has been suggested mainly as injury trigger. However, mechanoporation thresholds of generic membranes seem not to overlap with the axonal injury deformation range and microtubules appear too stiff and too weakly connected to undergo mechanical breaking. Here, we aim to shed a light on the mechanism of primary axonal injury, bridging finite element and molecular dynamics simulations. Despite the necessary level of approximation, our models can accurately describe the mechanical behavior of the unmyelinated axon and its membrane. More importantly, they give access to quantities that would be inaccessible with an experimental approach. We show that in a typical injury scenario, the axonal cortex sustains deformations large enough to entail pore formation in the adjoining lipid bilayer. The observed axonal deformation of 10-12% agree well with the thresholds proposed in the literature for axonal injury and, above all, allow us to provide quantitative evidences that do not exclude pore formation in the membrane as a result of trauma. Our findings bring to an increased knowledge of axonal injury mechanism that will have positive implications for the prevention and treatment of brain injuries.
PubMed: 32082244
DOI: 10.3389/fneur.2020.00025 -
Journal of Neurology, Neurosurgery, and... Mar 1998
Review
Topics: Animals; Axonal Transport; Axons; Axotomy; Brain Injuries; Cell Membrane; Cell Membrane Permeability; Cytoskeleton; Disease Models, Animal; Humans; Retrograde Degeneration
PubMed: 9527135
DOI: 10.1136/jnnp.64.3.285 -
Journal of Lipid Research Feb 1981The lipid composition was determined for axolemma-enriched fractions and myelin which were isolated via a preparation of purified myelinated axons. The myelin had a...
The lipid composition was determined for axolemma-enriched fractions and myelin which were isolated via a preparation of purified myelinated axons. The myelin had a lipid composition which was compatible with that previously reported for myelin isolated by alternative procedures. The most dense axolemma-enriched fraction contained 25.3% cholesterol, 25.8% galactolipid (21.3% cerebrosides and 4.8% sulfatides), and 48.9% phospholipid. The major phospholipids were the ethanolamine phospholipid (19.8% of total lipid weight; 49.0% in the plasmalogen form) and choline phospholipids (18.7% of total lipid weight; 16.0% in the plasmalogen form) with lesser amounts of sphingomyelin, phosphatidylserine, and phosphatidylinositol also present; the ganglioside content was 13.9 micrograms of acetylneuraminic acid per mg protein. The less dense axolemma-enriched fraction had a lipid composition which was intermediate between that of myelin and the more dense axolemma-enriched fraction. On the average, less than 2.3% of the total protein in the axolemma-enriched fraction was myelin basic protein. Both axolemma-enriched fractions stained uniformly with Luxol fast blue and demonstrated specific saxitoxin-binding which was enriched 2- to 7-fold over that of the whole white matter homogenate from which the fractions were isolated. The choline and ethanolamine phospholipids in that most dense axolemma-enriched fractions contained a greater percentage of unsaturated fatty acids compared with the comparable phospholipids in myelin. The content of unsaturated fatty acids in these phospholipids of the axolemma-enriched fraction was not as great as that of human CNS synaptic plasma membranes. However, the chain length distribution of these phospholipid fatty acids was similar in myelin, synaptic plasma membrane, and the axolemma-enriched fraction. The distribution of aldehydes derived from the ethanolamine phospholipids of the more dense axolemma-enriched fraction closely resemble the distribution of the comparable aldehydes in the myelin fraction. The possible origin and function of the lipids in the axolemma-enriched fractions are discussed.
Topics: Aged; Axons; Brain Chemistry; Fatty Acids; Humans; Membrane Lipids; Middle Aged; Myelin Sheath; Phosphatidylcholines; Phosphatidylethanolamines; Saxitoxin; Subcellular Fractions
PubMed: 7240954
DOI: No ID Found -
Brain Sciences Nov 2023Diffuse axonal injury (DAI) is a significant feature of traumatic brain injury (TBI) across all injury severities and is driven by the primary mechanical insult and... (Review)
Review
Diffuse axonal injury (DAI) is a significant feature of traumatic brain injury (TBI) across all injury severities and is driven by the primary mechanical insult and secondary biochemical injury phases. Axons comprise an outer cell membrane, the axolemma which is anchored to the cytoskeletal network with spectrin tetramers and actin rings. Neurofilaments act as space-filling structural polymers that surround the central core of microtubules, which facilitate axonal transport. TBI has differential effects on these cytoskeletal components, with axons in the same white matter tract showing a range of different cytoskeletal and axolemma alterations with different patterns of temporal evolution. These require different antibodies for detection in post-mortem tissue. Here, a comprehensive discussion of the evolution of axonal injury within different cytoskeletal elements is provided, alongside the most appropriate methods of detection and their temporal profiles. Accumulation of amyloid precursor protein (APP) as a result of disruption of axonal transport due to microtubule failure remains the most sensitive marker of axonal injury, both acutely and chronically. However, a subset of injured axons demonstrate different pathology, which cannot be detected via APP immunoreactivity, including degradation of spectrin and alterations in neurofilaments. Furthermore, recent work has highlighted the node of Ranvier and the axon initial segment as particularly vulnerable sites to axonal injury, with loss of sodium channels persisting beyond the acute phase post-injury in axons without APP pathology. Given the heterogenous response of axons to TBI, further characterization is required in the chronic phase to understand how axonal injury evolves temporally, which may help inform pharmacological interventions.
PubMed: 38002566
DOI: 10.3390/brainsci13111607 -
Annals of Neurology May 1984The mechanisms responsible for the induction of Schwann cell proliferation in peripheral nerves undergoing wallerian degeneration and segmental demyelination are not... (Comparative Study)
Comparative Study
The mechanisms responsible for the induction of Schwann cell proliferation in peripheral nerves undergoing wallerian degeneration and segmental demyelination are not understood. To determine whether contact with axolemma stimulates mitosis of human Schwann cells, cultured Schwann cells from spinal roots obtained postmortem and from sural nerve biopsy specimens were incubated with axolemmal fractions prepared from human spinal cord or from adult rat central nervous system. Schwann cell proliferation was estimated by autoradiographic assay of tritiated thymidine incorporation. Schwann cell labeling indices after exposure to human or rat axolemmal fractions ranged from 26.7 to 59.9%; labeling indices of Schwann cells cultured without axolemmal fraction were 9.8 to 22.4%. The stimulation index, or ratio of Schwann cell labeling index with axolemmal fraction to that without axolemmal fraction, ranged from 1.97 to 3.40. This study demonstrates that both human and rat axolemma are capable of stimulating human Schwann cell replication in vitro.
Topics: Adolescent; Adult; Animals; Axons; Cell Division; Cell Membrane; Cells, Cultured; Child; Female; Humans; Male; Middle Aged; Mitogens; Nerve Degeneration; Peripheral Nervous System Diseases; Rats; Schwann Cells
PubMed: 6329072
DOI: 10.1002/ana.410150508 -
The Journal of General Physiology May 1961Previous electron microscope studies have shown that the Schwann cell layer is traversed by long and tortuous slit-like channels approximately 60A wide, which provide...
Previous electron microscope studies have shown that the Schwann cell layer is traversed by long and tortuous slit-like channels approximately 60A wide, which provide the major route of access to the axolemma surface. In the present work the restriction offered by the resting axolemma to the passage of six small non-electrolyte molecules has been determined. The radii of the probing molecules were estimated from constructed molecular models. The ability of the axolemma to discriminate between the solvent (water) and each probing molecule was expressed in terms of the reflection coefficient sigma. sigma was then used to calculate an effective pore size for the resting axolemma. The value of 4.25 A found for the pore radius is in excellent agreement with the 1.5 to 8.5 A limiting values previously calculated from our measurements of water fluxes. The presence of pores with 4.25 A radius in the resting axolemma is compatible with restricted diffusion of Na. The present paper leads to the conclusion that the axolemma is the only continuous barrier across which the ionic gradient responsible for the normal functioning of the nerve can be maintained. The combined findings of electron microscopy, water permeability, and molecular restricted filtration indicate that in all probability the axolemma is the "excitable membrane" of the physiologists.
Topics: Animals; Axons; Decapodiformes; Ions; Microscopy, Electron; Neurons; Permeability; Sodium; Water
PubMed: 13781431
DOI: 10.1085/jgp.44.5.963 -
International Review of Neurobiology 1983
Review
Topics: Aging; Animals; Axons; Electric Conductivity; Freeze Fracturing; Microscopy, Electron; Myelin Sheath; Neuroglia; Neurons; Optic Nerve; Rats; Rats, Inbred Strains; Retina
PubMed: 6360938
DOI: 10.1016/s0074-7742(08)60226-3