scholarly journals Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier

2020 ◽  
Vol 64 (2) ◽  
Author(s):  
Elena Pompili ◽  
Viviana Ciraci ◽  
Stefano Leone ◽  
Valerio De Franchis ◽  
Pietro Familiari ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves ◽  
Axonal Regeneration ◽  
Opposite Effect ◽  
Ex Vivo ◽  
Axon Growth ◽  
Coagulation Cascade ◽  
Protease Activated Receptor 1 ◽  
Low Levels ◽  
Stimulation Of

Schwann cells (SC) are characterized by a remarkable plasticity that enables them to promptly respond to nerve injury promoting axonal regeneration. In peripheral nerves after damage SC convert to a repair-promoting phenotype activating a sequence of supportive functions that drive myelin clearance, prevent neuronal death, and help axon growth and guidance. Regeneration of peripheral nerves after damage correlates inversely with thrombin levels. Thrombin is not only the key regulator of the coagulation cascade but also a protease with hormone-like activities that affects various cells of the central and peripheral nervous system mainly through the protease-activated receptor 1 (PAR1). Aim of the present study was to investigate if and how thrombin could affect the axon supportive functions of SC. In particular, our results show that the activation of PAR1 in rat SC cultures with low levels of thrombin or PAR1 agonist peptides induces the release of molecules, which favor neuronal survival and neurite elongation. Conversely, the stimulation of SC with high levels of thrombin or PAR1 agonist peptides drives an opposite effect inducing SC to release factors that inhibit the extension of neurites. Moreover, high levels of thrombin administered to sciatic nerve ex vivo explants induce a dramatic change in SC morphology causing disappearance of the Cajal bands, enlargement of the Schmidt-Lanterman incisures and calcium-mediated demyelination of the paranodes. Our results indicate thrombin as a novel modulator of SC plasticity potentially able to favor or inhibit SC pro-regenerative properties according to its level at the site of lesion.

scholarly journals Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Laura J Wagstaff ◽  
Jose A Gomez-Sanchez ◽  
Shaline V Fazal ◽  
Georg W Otto ◽  
Alastair M Kilpatrick ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Axonal Regeneration ◽  
Nerve Repair ◽  
Axon Growth ◽  
Common Mechanism ◽  
Molecular Pathways ◽  
Chronic Denervation ◽  
Clinical Problems ◽  
Molecular Framework

After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS.

Regulation of protease-activated receptor 1 (PAR1) on platelets and responsiveness to thrombin receptor activating peptide (TRAP) during systemic inflammation in humans

2003 ◽  
Vol 90 (11) ◽  
pp. 898-903 ◽  
Author(s):  
Rosemarie Reiter ◽  
Ulla Derhaschnig ◽  
Alexander Spiel ◽  
Priska Keen ◽  
Francesco Cardona ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Human Platelets ◽  
Thrombin Receptor ◽  
Protease Activated Receptors ◽  
Human Endotoxemia ◽  
Protease Activated Receptor 1 ◽  
Stimulation Of ◽  
Thrombin Formation

SummaryThrombin is a coagulation protease that activates platelets, endothelial cells, leukocytes and mesenchymal cells. Thrombin signaling is mediated at least in part by protease-activated receptors (PARs). As little is known about the in vivoregulation of PAR1, this study aimed to characterize the effects of systemic thrombin formation during human endotoxemia on the regulation of PAR1 and the associated responsiveness of human platelets to thrombin receptor activating peptide (TRAP). Endotoxin (2 ng/kg) was infused into 40 healthy men to study the regulation of PAR1 in systemic human inflammation. The SPAN12 antibody was used to determine the in vivoregulation of PAR1. To measure whether modulation of the PAR1 receptor may be associated with altered platelet reactivity, whole blood was stimulated with TRAP ex vivo. Thrombin generation was determined by prothrombin (F1+2) fragment. F1+2levels increased almost 9-fold from 0.5±0.1 nmol/L to 4.5±1.9 nmol/L at 4 h (p<0.001). PAR1 decreased by ~8% (p<0.001) within 2 h after endotoxin infusion and stayed at those levels until 6 h. Concomitantly, TRAP induced P-selectin expression maximally decreased by 18% (p<0.001) at 6 h. In conclusion, PAR1 expression is down-regulated on platelets during systemic thrombin formation induced by inflammation in humans which results in decreased responsiveness to subsequent stimulation of the PAR1 receptor.

A Morphological Study of Schwann Cells and Axonal Regeneration in Chronically Transected Human Peripheral Nerves

1998 ◽  
Vol 23 (5) ◽  
pp. 583-587 ◽  
Author(s):  
G. TERENGHI ◽  
J. S. CALDER ◽  
R. BIRCH ◽  
S. M. HALL
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves ◽  
Axonal Regeneration ◽  
Morphological Study ◽  
Light And Electron Microscopy ◽  
Experimental Models ◽  
Distal Stump ◽  
Nerve Reconstruction ◽  
Severe Injuries ◽  
Distal Nerve

Relatively little is known about the effects of chronic transection on human peripheral nerves. In this study intraoperative biopsies were obtained from proximal and distal nerve stumps and intervening neuromas resected before peripheral nerve reconstruction. Biopsies were collected from ten patients following differing types of nerve injury, with delays to repair ranging from 8 to 53 months. Nerves were examined by light and electron microscopy. In general, reinnervation was poor, although even following the most severe injuries, all of the distal stumps contained some regrowing axons, which were always associated with Schwann cells. Denervated Schwann cells, arranged in typical bands of Bungner were consistently present in each distal stump. Our findings confirm that the morphology of chronically denervated human peripheral nerves is essentially similar to that described in experimental models.

scholarly journals Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1668
Author(s):  
Elena Pompili ◽  
Valerio De Franchis ◽  
Claudia Giampietri ◽  
Stefano Leone ◽  
Elena De Santis ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Tissue Injury ◽  
Membrane Receptors ◽  
Protease Activated Receptors ◽  
Cell Plasma ◽  
Ability To Regenerate ◽  
Protease Activated Receptor 1 ◽  
Plasma Membrane Receptors

In contrast with the brain and spinal cord, peripheral nerves possess a striking ability to regenerate after damage. This characteristic of the peripheral nervous system is mainly due to a specific population of glial cells, the Schwann cells. Schwann cells promptly activate after nerve injury, dedifferentiate assuming a repair phenotype, and assist axon regrowth. In general, tissue injury determines the release of a variety of proteases which, in parallel with the degradation of their specific targets, also activate plasma membrane receptors known as protease-activated receptors (PARs). PAR1, the prototypical member of the PAR family, is also known as thrombin receptor and is present at the Schwann cell plasma membrane. This receptor is emerging as a possible regulator of the pro-regenerative capacity of Schwann cells. Here, we summarize the most recent literature data describing the possible contribution of PAR1 and PAR1-activating proteases in regulating the regeneration of peripheral nerves.

Early Platelet-Collagen Interactions in Whole Blood and Their Modifications by Aspirin and Dipyridamole Evaluated by a New Method (Basic Wave)

1985 ◽  
Vol 54 (04) ◽  
pp. 799-803 ◽  
Author(s):  
José Luís Pérez-Requejo ◽  
Justo Aznar ◽  
M Teresa Santos ◽  
Juana Vallés
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
White Blood Cells ◽  
Reversible Aggregation ◽  
Inhibitory Compounds ◽  
Rapid Generation ◽  
Stimulation Of ◽  
Collagen Stimulation

SummaryIt is shown that the supernatant of unstirred whole blood at 37° C, stimulated by 1 μg/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC’s intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes “ex vivo” the ability of whole blood and PRP to generate BASIC waves and dipyridamole “in vitro” significantly reduces BASIC’s intensity in whole blood in every tested sample, but shows little effect in PRP.

scholarly journals Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo

The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano
Keyword(s):  
Lymph Node ◽  
Targeted Delivery ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Tissue Slices ◽  
Microfluidic Platform ◽  
Spatially Resolved ◽  
Local Stimulation ◽  
Stimulation Of

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.

Surface anodal stimulation of human peripheral nerves

1988 ◽  
Vol 73 (3) ◽  
pp. 481-488 ◽  
Author(s):  
T. Winkler ◽  
E. St�lberg
Keyword(s):  
Peripheral Nerves ◽  
Anodal Stimulation ◽  
Stimulation Of

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

2012 ◽  
Vol 107 (10) ◽  
pp. 2742-2755 ◽  
Author(s):  
Max Eickenscheidt ◽  
Martin Jenkner ◽  
Roland Thewes ◽  
Peter Fromherz ◽  
Günther Zeck
Keyword(s):  
Electrical Stimulation ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Biophysical Model ◽  
Retinal Neurons ◽  
Direct Stimulation ◽  
Tungsten Electrode ◽  
Partial Restoration ◽  
Low Amplitude ◽  
Stimulation Of

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array—insulated by an inert oxide—allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.

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