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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 -
Journal of the Peripheral Nervous... Jul 2023Action potential propagation along myelinated axons depends on the geometry of the myelin unit and the division of the underlying axon to specialized domains. The latter... (Review)
Review
Action potential propagation along myelinated axons depends on the geometry of the myelin unit and the division of the underlying axon to specialized domains. The latter include the nodes of Ranvier (NOR), the paranodal junction (PNJ) flanking the nodes, and the adjacent juxtaparanodal region that is located below the compact myelin of the internode. Each of these domains contains a unique composition of axoglial adhesion molecules (CAMs) and cytoskeletal scaffolding proteins, which together direct the placement of specific ion channels at the nodal and juxtaparanodal axolemma. In the last decade it has become increasingly clear that antibodies to some of these axoglial CAMs cause immune-mediated neuropathies. In the current review we detail the molecular composition of the NOR and adjacent membrane domains, describe the function of different CAM complexes that mediate axon-glia interactions along the myelin unit, and discuss their involvement and the underlying mechanisms taking place in peripheral nerve pathologies. This growing group of pathologies represent a new type of neuropathies termed "nodopathies" or "paranodopathies" that are characterized by unique clinical and molecular features which together reflect the mechanisms underlying the molecular assembly and maintenance of this specialized membrane domain.
Topics: Humans; Ranvier's Nodes; Axons; Myelin Sheath; Neuroglia; Peripheral Nerves
PubMed: 37272548
DOI: 10.1111/jns.12568 -
Annals of Translational Medicine Apr 2023Gangliosides are a class of glycosphingolipid molecules that are highly enriched in cellular membranes of the nervous system. The gangliosides associated with autoimmune... (Review)
Review
Gangliosides are a class of glycosphingolipid molecules that are highly enriched in cellular membranes of the nervous system. The gangliosides associated with autoimmune diseases of the nervous system are mainly GM1, GD1a, GalNAc-GD1a, GM1b, GD3, CD1b, GT1a, and GQ1b. Multiple antibodies recognizing gangliosides are associated with some acute or chronic peripheral neuropathies, especially Guillain-Barré syndrome (GBS) and its clinical variants. Antibodies binding to gangliosides can activate complement system and recruit macrophages on the axolemma at the nodes of Ranvier of motor fibers, which are found in the course of GBS, causing axonal degeneration and reversible conduction block or conduction failure. Testing of anti-gangliosides autoantibodies is helpful for diagnosis of autoimmune peripheral neuropathies or support the diagnosis of the subtypes. These anti-gangliosides antibodies are usually detected by several qualitative or quantitative methods, particularly enzyme-linked immunosorbent assay (ELISA) and immunodot assays, which have been commercialized or established in-house worldwide. Herein, we introduce the methods and clinical applications of these assays in the diagnosis of autoimmune peripheral neuropathies. Anti-gangliosides antibodies are diagnostic markers of GBS subtypes. We use GBS as an example to explain the role of anti-gangliosides antibodies in the pathogenesis and diagnostic classification of neuropathies.
PubMed: 37090048
DOI: 10.21037/atm-20-2285 -
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 -
Progress in Molecular Biology and... 2018Gangliosides are a family of sialic acid-containing glycosphingolipids highly expressed in the nervous system of vertebrates. Over the last 25years, research has... (Review)
Review
Gangliosides are a family of sialic acid-containing glycosphingolipids highly expressed in the nervous system of vertebrates. Over the last 25years, research has unmasked several of their neurobiological functions but the role of gangliosides in the nervous system remains not fully elucidated. Genetic disruption of genes for key enzymes involved in ganglioside biosynthesis led to the discovery of their diverse functions and highlighted the exquisite structural specificity required in this processes. In the nervous system, gangliosides regulate axonal caliber and organize ion channels at the nodes of Ranvier, a critical step to ensure fast conduction velocity of myelinated fibers. They also act as receptors for lectins located on apposing myelin membranes critical to maintain axon-glia interactions that result in cytoskeleton stabilization. After a lesion, gangliosides acting as receptors for glial-derived molecules present in the extracellular milieu can halt axon regeneration. Similarly, antiganglioside antibodies present in autoimmune neurological conditions can mimic this inhibitory effect on nerve repair. Studying the molecular details of the molecular interaction of gangliosides in trans with ligands present on apposing cell membranes and receptor/transducer molecules in cis interaction at the axolemma membrane, together with their downstream signaling pathways, represent a unique opportunity to expand our knowledge about the role of gangliosides in the nervous system.
Topics: Animals; Axons; Gangliosides; Humans; Regeneration; Signal Transduction
PubMed: 29747821
DOI: 10.1016/bs.pmbts.2018.03.001 -
Neuroscience Research Mar 2017Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials... (Review)
Review
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria. Disruption of excitable domains and altered distribution of functional elements in CNS axons is associated with demyelinating diseases such as multiple sclerosis, and is likely a mechanism common to other neurological disorders. This review will provide a brief overview of the molecular structure of the AIS and nodes of Ranvier, as well as the distribution of mitochondria in myelinated axons. In addition, this review highlights important structural and functional changes within myelinated CNS axons that are associated with neurological dysfunction.
Topics: Action Potentials; Alzheimer Disease; Animals; Axons; Brain Injuries; Calpain; Central Nervous System; Humans; Mitochondria; Multiple Sclerosis; Myelin Sheath; Ranvier's Nodes
PubMed: 27717670
DOI: 10.1016/j.neures.2016.09.010 -
Neural Regeneration Research Apr 2016The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of... (Review)
Review
The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily repaired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.
PubMed: 27212898
DOI: 10.4103/1673-5374.180724