-
Journal of Clinical Neurology (Seoul,... Mar 2023Peripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in...
BACKGROUND AND PURPOSE
Peripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD.
METHODS
The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength-duration time constant, threshold electrotonus (TE), current-threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group).
RESULTS
In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40-60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; =20) than in the NC group (54.5%±0.7%, =25; <0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; =0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (=25) also showed no differences in either the motor or sensory NETs.
CONCLUSIONS
The pattern of excitability in COPD revealed a membrane depolarization attributable to Na-K-ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.
PubMed: 36854335
DOI: 10.3988/jcn.2022.0249 -
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 -
Journal of Endodontics Nov 2022Information on the type of vesicular glutamate transporter (VGLUT) that is expressed in the Piezo2-positive (Piezo2+) neurons in the trigeminal ganglion (TG) and on the...
INTRODUCTION
Information on the type of vesicular glutamate transporter (VGLUT) that is expressed in the Piezo2-positive (Piezo2+) neurons in the trigeminal ganglion (TG) and on the type of Piezo2+ axons and their distribution in the dental pulp is important for understanding dental pain elicited by mechanical stimuli and developing new therapeutic strategies.
METHODS
We examined the expression of Piezo2 and its coexpression with VGLUT1 and VGLUT2 in rat TG, the sensory root, and human dental pulp using light and electron microscopic immunohistochemistry and quantitative analysis.
RESULTS
VGLUT1 and VGLUT2 were expressed in the TG neurons. Piezo2 was expressed in axons of all types but primarily in small myelinated (Aδ) axons in the sensory root. In the dental pulp, Piezo2 was expressed densely in the numerous axons that form a plexus in the peripheral pulp. Piezo2+ axons in the peripheral pulp were mostly unmyelinated, and Piezo2 immunoreactivity was often concentrated near the axolemma, suggesting that it may represent functional receptors.
CONCLUSIONS
These findings suggest that VGLUT1 and VGLUT2 are involved in the glutamate signaling in Piezo2+ neurons, Piezo2 may be primarily activated by noxious mechanical stimuli, and Piezo2-mediated dental mechanotransduction may be primarily elicited in the peripheral pulp.
Topics: Rats; Humans; Animals; Trigeminal Ganglion; Vesicular Glutamate Transport Proteins; Vesicular Glutamate Transport Protein 2; Dental Pulp; Mechanotransduction, Cellular; Vesicular Monoamine Transport Proteins; Rats, Sprague-Dawley; Glutamates; Ion Channels
PubMed: 35952898
DOI: 10.1016/j.joen.2022.07.012 -
Neurologia 2022Guillain-Barré syndrome (GBS) is an acute-onset, immune-mediated disease of the peripheral nervous system. It may be classified into 2 main subtypes: demyelinating... (Review)
Review
INTRODUCTION
Guillain-Barré syndrome (GBS) is an acute-onset, immune-mediated disease of the peripheral nervous system. It may be classified into 2 main subtypes: demyelinating (AIDP) and axonal (AMAN). This study aims to analyse the mechanisms of axonal damage in the early stages of GBS (within 10 days of onset).
DEVELOPMENT
We analysed histological, electrophysiological, and imaging findings from patients with AIDP and AMAN, and compared them to those of an animal model of myelin P2 protein-induced experimental allergic neuritis. Inflammatory oedema of the spinal nerve roots and spinal nerves is the initial lesion in GBS. The spinal nerves of patients with fatal AIDP may show ischaemic lesions in the endoneurium, which suggests that endoneurial inflammation may increase endoneurial fluid pressure, reducing transperineurial blood flow, potentially leading to conduction failure and eventually to axonal degeneration. In patients with AMAN associated with anti-ganglioside antibodies, nerve conduction block secondary to nodal sodium channel dysfunction may affect the proximal, intermediate, and distal nerve trunks. In addition to the mechanisms involved in AIDP, active axonal degeneration in AMAN may be associated with nodal axolemma disruption caused by anti-ganglioside antibodies.
CONCLUSION
Inflammatory oedema of the proximal nerve trunks can be observed in early stages of GBS, and it may cause nerve conduction failure and active axonal degeneration.
Topics: Amantadine; Animals; Axons; Guillain-Barre Syndrome; Neural Conduction; Peripheral Nerves
PubMed: 35779867
DOI: 10.1016/j.nrleng.2020.08.001 -
Journal of the Neurological Sciences Jul 2022To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier.
OBJECTIVE
To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier.
STUDY DESIGN AND SETTING
We performed the pathological study (nerve biopsy of a sural nerve) of two patients, one with an acute form of ataxic peripheral neuropathy called 'Miller Fisher syndrome' (MFS), the other one with a chronic form called 'chronic ataxic neuropathies with disialosyl antibodies' (CANDA).
RESULTS
A dysimmune process involving peripheral nerves commences in myelin, at the internodal area or/and in the paranodal and nodal regions. Our electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.
CONCLUSION
Many of the immune-mediated peripheral neuropathies are now classified as nodoparanodopathies. This subtype of auto-immune neuropathy may present various clinical phenotypes such as 'Acute Motor Axonal Neuropathy' (AMAN), 'Acute Motor and Sensory Neuropathy' (AMSAN) or 'chronic inflammatory demyelinating polyradiculoneuropathy' (CIDP), and are associated with anti-disialosyl antibodies. In our two cases, some paranodes seem to be associated with macrophages and we hypothesized that these lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region due to disialosyl antibodies against gangliosides which are mainly located at the level of the axolemma of the paranode.
Topics: Antibodies; Ataxia; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 35576641
DOI: 10.1016/j.jns.2022.120279 -
Scientific Reports Dec 2021The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment...
The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.
Topics: Adult; Female; Humans; Limit of Detection; Male; Microscopy, Electron; Middle Aged; Myelin Sheath; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Vagus Nerve
PubMed: 34903749
DOI: 10.1038/s41598-021-03248-1 -
Neural Regeneration Research May 2022The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral...
The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral nerve regeneration. However, little is known about how the extracellular matrix (ECM) microenvironment affects this process. Here, we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrix-gel, Matrigel, laminin 521, collagen I, and collagen IV, and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment. We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon. A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation. Collagen VI interacted with NCAM1 by directly binding to the FNIII domain, thereby increasing the stability of NCAM1 at the axolemma. Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/mL Matrigel and 20 μg/mL collagen VI. These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation. This study was approved by the Animal Ethics Committee of Guangzhou Medical University (approval No. GY2019048) on April 30, 2019.
PubMed: 34558529
DOI: 10.4103/1673-5374.324861 -
The Journal of Physiology Oct 2021In myelinated nerve fibres, action potentials are generated at nodes of Ranvier. These structures are located at interruptions of the myelin sheath, forming narrow gaps...
In myelinated nerve fibres, action potentials are generated at nodes of Ranvier. These structures are located at interruptions of the myelin sheath, forming narrow gaps with small rings of axolemma freely exposed to the extracellular space. The mammalian node contains a high density of Na channels and K -selective leakage channels. Voltage-dependent Kv1 channels are only present in the juxta-paranode. Recently, the leakage channels have been identified as K2P channels (TRAAK, TREK-1). K2P channels are K -selective 'background' channels, characterized by outward rectification and their ability to be activated, e.g. by temperature, mechanical stretch or arachidonic acid. We are only beginning to elucidate the peculiar functions of nodal K2P channels. I will discuss two functions of the nodal K2P-mediated conductance. First, at body temperature K2P channels have a high open probability, thereby inducing a resting potential of about -85 mV. This negative resting potential reduces steady-state Na channel inactivation and ensures a large Na inward current upon a depolarizing stimulus. Second, the K2P conductance is involved in nodal action potential repolarization. The identification of nodal K2P channels is exciting since it shows that the nodal K conductance is not a fixed value but can be changed: it can be increased or decreased by a broad range of K2P modulators, thereby modulating, for example, the resting potential. The functional importance of nodal K2P channels will be exemplified by describing in more detail the function of the K2P conductance increase by raising the temperature from room temperature to 37°C.
Topics: Action Potentials; Animals; Axons; Membrane Potentials; Myelin Sheath; Nerve Fibers, Myelinated
PubMed: 34425634
DOI: 10.1113/JP281723 -
Frontiers in Molecular Biosciences 2021Around half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been...
Around half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been suggested as possible injury trigger. Here, we have used molecular models to have a better insight on the structural and mechanical properties of axon sub-cellular components. We modelled myelin sheath and node of Ranvier as lipid bilayers at a coarse grained level. We built ex-novo a model for the myelin. Lipid composition and lipid saturation were based on the available experimental data. The model contains 17 different types of lipids, distributed asymmetrically between two leaflets. Molecular dynamics simulations were performed to characterize the myelin and node-of-Ranvier bilayers at equilibrium and under deformation and compared to previous axolemma simulations. We found that the myelin bilayer has a slightly higher area compressibility modulus and higher rupture strain than node of Ranvier. Compared to the axolemma in unmyelinated axon, mechanoporation occurs at 50% higher strain in the myelin and at 23% lower strain in the node of Ranvier in myelinated axon. Combining the results with finite element simulations of the axon, we hypothesizes that myelin does not rupture at the thresholds proposed in the literature for axonal injury while rupture may occur at the node of Ranvier. The findings contribute to increases our knowledge of axonal sub-cellular components and help to understand better the mechanism behind axonal brain injury.
PubMed: 34250015
DOI: 10.3389/fmolb.2021.669897