scholarly journals Glial TGFβ activity promotes axon survival in peripheral nerves

2021 ◽  
Author(s):  
Alex Lassetter ◽  
Megan Corty ◽  
Romina Barria ◽  
Amy Sheehan ◽  
Sue Aicher ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Tgfβ Signaling ◽  
Age Dependent ◽  
Support Mechanisms ◽  
Axon Survival ◽  
Tgfβ Superfamily

Axons can represent the majority of the volume of a neuron and are energetically very demanding. Specialized glia ensheathe axons and are believed to support axon function and maintenance throughout life, but molecular details of glia-neuron support mechanisms remain poorly defined. Here we identify a collection of secreted and transmembrane genes that are required in glia for long-term axon survival in vivo. We show that key components of the TGFβ superfamily are required cell-autonomously in glia for peripheral nerve maintenance, although their loss does not disrupt glial morphology. We observe age-dependent neurodegeneration in the absence of glial TGFβ signaling that can be rescued by genetic blockade of Wallerian degeneration. Our data argue that glial TGFβ signaling normally acts to promote axon survival and suppress neurodegeneration.

Individual mechanisms underlying peripheral nerve damage when exposed to metallic mercury

2020 ◽  
Vol 60 (12) ◽  
pp. 918-924
Author(s):  
Dina V. Rusanova ◽  
Oleg L. Lakhman ◽  
Galina M. Bodienkova ◽  
Irina V. Kudaeva ◽  
Natalya G. Kuptsova
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Blood Circulation ◽  
The State ◽  
Contact Period ◽  
Peripheral Nerve Damage ◽  
Demyelinating Disorders ◽  
Peripheral Blood Circulation ◽  
Antibodies To Dna

Introduction. There is a lack of knowledge of the pathophysiological mechanisms that form peripheral nerve disorders in mercury lesions of professional origin. The study aims to reveal the mechanisms underlying peripheral nerve damage in the long-term post-contact period of chronic mercury intoxication (CMI). Materials and methods. Fifty-one people had the diagnosis of a long-term period of CMI. The post-contact period was 8.5±2.6 years. The authors compared the results with a control group of 26 healthy men who had no contact with toxic substances. Stimulating electroneuromyography was performed. We studied the body systems that could contribute to the formation of disorders in the peripheral nerves. Changes in peripheral hemodynamics were studied using reovasography. The content of autoantibodies, neuron-specific enolase, serotonin, histamine, catecholamines (epinephrine, dopamine), metanephrine, and neurotrophin-3 was reviewed. The content of ceruloplasmin, secondary products of lipid peroxidation processes, reduced glutathione, the activity of superoxide dismutase and the content of nitric oxide levels were determined. Results. The study established pathogenetic structural links of peripheral nerve disorders. The autoimmune process's role was to increase the range of antibodies to the MAG protein and increase the level of antibodies to DNA. Violations of elastic-tonic properties of peripheral vessels could be associated with the functional state of motor axons. The increased content of neurotransmitters is related to the state of peripheral blood circulation; the most pronounced changes were on the legs, which could contribute to the occurrence and maintenance of vasoconstriction. The role of oxidative stress in the formation of demyelinating disorders in patients' peripheral nerves in the long-term period of CRI is possible. Conclusion. Neuroimmunological processes has an essential role in the development of peripheral nerve demyelination was shown, which consists in an increase in the content of antibodies to the MAG protein expressed on Schwann cells of peripheral nerves and in an increase in the level of antibodies to DNA involved in the formation of demyelinating changes when exposed to metallic mercury. The revealed pathological changes in the state of the peripheral blood circulation, characterized by a violation of the vessels' elastic-tonic properties, leading to demyelination of motor axons in patients in the long-term period of CMI. The increased content of neurotransmitters in the examined is of great importance in the state of peripheral circulation. Pronounced changes in blood circulation are established on the lower extremities, which may be associated with the predominance of α-adrenergic receptors in the arterial bed and may contribute to the occurrence and maintenance of vasoconstriction in the legs. The relationship between changes in indicators of oxidative stress, consisting of a decrease in the value of superoxide dismutase and reduced glutathione, and the formation of demyelinating disorders of peripheral nerves in patients in the long-term period of CMI has been proved.

scholarly journals ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Junyang Jung ◽  
Hyun Woo Jo ◽  
Hyunseob Kwon ◽  
Na Young Jeong
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Atp Release ◽  
Nerve Degeneration ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Axonal Degradation

Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5′-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome.

Earthworm Extracts Facilitate PC12 Cell Differentiation and Promote Axonal Sprouting in Peripheral Nerve Injury

2010 ◽  
Vol 38 (03) ◽  
pp. 547-560 ◽  
Author(s):  
Chao-Tsung Chen ◽  
Jaung-Geng Lin ◽  
Tung-Wu Lu ◽  
Fuu-Jen Tsai ◽  
Chih-Yang Huang ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Peripheral Nerve Regeneration ◽  
In Vitro Study ◽  
Potential Growth ◽  
Marked Enhancement ◽  
Growth Promoting ◽  
Success Percentage

The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 μg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves.

Chronic effects of muscle and nerve-directed stretching on tissue mechanics

2020 ◽  
Vol 129 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ricardo J. Andrade ◽  
Sandro R. Freitas ◽  
François Hug ◽  
Guillaume Le Sant ◽  
Lilian Lacourpaille ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Tissue Mechanics ◽  
Plantar Flexor ◽  
Chronic Effects ◽  
Flexor Muscles ◽  
Plantar Flexor Muscles

This study demonstrates that the mechanical properties of plantar flexor muscles and sciatic nerve can adapt mechanically to long-term stretching programs. Although interventions targeting muscular or nonmuscular structures are both effective at increasing maximal range of motion, the changes in tissue mechanical properties (stiffness) are specific to the structure being preferentially stretched by each program. We provide the first in vivo evidence that stiffness of peripheral nerves adapts to long-term loading stimuli using appropriate nerve-directed stretching.

Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts

Neuroscience ◽  
2011 ◽  
Vol 181 ◽  
pp. 278-291 ◽  
Author(s):  
P.G. di Summa ◽  
D.F. Kalbermatten ◽  
E. Pralong ◽  
W. Raffoul ◽  
P.J. Kingham ◽  
...  
Keyword(s):  
Peripheral Nerves ◽  
Nerve Grafts

Early events of peripheral nerve regeneration

2005 ◽  
Vol 2 (2) ◽  
pp. 139-147 ◽  
Author(s):  
DAVID MCDONALD ◽  
CHU CHENG ◽  
YUANYUAN CHEN ◽  
DOUGLAS ZOCHODNE
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
De Novo ◽  
Peripheral Nerve Regeneration ◽  
Confocal Imaging ◽  
Double Labeling ◽  
Proximal Stump ◽  
Cell Processes ◽  
Early Regeneration

Early regeneration of injured peripheral nerves involves a series of events that are important in the success of eventual reconnection. In many nerve injuries, such as transections with gaps, axons and Schwann cells (SCs) penetrate into new microenvironments de novo, not involving zones of Wallerian degeneration. We studied unexplored axon–SC interactions by sampling of newly forming connections through a silicone conduit across transected rat sciatic peripheral nerve gaps. Axon and SC participation in bridge formation was addressed by light microscopy, electron microscopy and by double-labeling immunohistochemistry, including confocal imaging, and several, less appreciated aspects of early regrowth were identified. There are limitations to early and widespread regeneration of axons and SCs into bridges initially formed from connective tissue and blood vessels. Regrowth is ‘staggered’ such that only a small percentage of parent axons sampled the early bridge. There is an intimate, almost invariable relationship between SCs and extension of axons, which challenges the concept that axons lead and SCs follow. ‘Naked’ axons were infrequent and limited in scope. Axons did not seek out and adhere to vascular laminin but intimately followed laminin deposits associated with apposed SCs. Growth cones identified by labeling of β III tubulin, PGP 9.5 and GAP43/B50 were complex, implying a pause in their regrowth, and were most prominent at the proximal stump–regenerative bridge interface. There is surprising and substantial hostility to local regrowth of axons into newly forming peripheral nerve bridges. Early axon outgrowth, associated with apposed Schwann cell processes, is highly constrained even when not exposed to adjacent myelin and products of Wallerian degeneration.

Biomaterials for Repairing Gaps After Peripheral Nerve Injury

2021 ◽  
Vol 13 (4) ◽  
pp. 530-536
Author(s):  
Dong-Xu Huang ◽  
Jiang-Nan Li ◽  
Ge-Yi Zhang ◽  
Wen-Gang Wang ◽  
Lei Xia ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Peripheral Nerve Injury ◽  
Wallerian Degeneration ◽  
Standard Treatment ◽  
Spontaneous Recovery ◽  
Nerve Conduits ◽  
Advanced Biomaterials ◽  
Review Current

Peripheral nerves have complex and precise structures that differ from other types of tissues and intrinsic regeneration abilities after injury. Spontaneous recovery is possible for neuropraxia and axonotmesis, while surgical treatment is required for neurotmesis. It remains a challenge to repair nerve gaps, a series of severe neurotmesis. It seems that 3 cm is the upper limit distance for primate peripheral nerves to regenerate spontaneously. Nerve autografts are the gold standard treatment for bridging nerve gaps. In the present review, current biomaterials for repairing gaps after peripheral nerve injury are briefly summarized. Moreover, the microstructure of the peripheral nerve, classifications of peripheral nerve injury, and the Wallerian degeneration are reviewed in the biological view and clinical practice. The failure of nerve regeneration in nerve conduits bridging longer than 3 cm gaps may be contributing to the insufficient vascularization of nerve conduit materials. Future researchers could focus on advanced biomaterials that promoting the angiogenesis of nerve conduits.

scholarly journals Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder

2005 ◽  
Vol 202 (6) ◽  
pp. 727-732 ◽  
Author(s):  
Leonardo Salmena ◽  
Razqallah Hakem
Keyword(s):  
T Cells ◽  
T Cell ◽  
Caspase 8 ◽  
Immune Disorder ◽  
Age Dependent ◽  
Lymphoproliferative Syndrome ◽  
Patient Prognosis ◽  
Specific Deletion

Caspase-8 is best known for its cell death function via death receptors. Recent evidence indicates that caspase-8 also has nonapoptotic functions. Caspase-8 deficiency is associated with pathologies that are unexpected for a proapoptotic molecule, such as abrogation of activation-induced lymphocyte proliferation, perturbed immune homeostasis, and immunodeficiency. In this study, we report the long-term physiological consequences of T cell–specific deletion of caspase-8 (tcasp8−/−). We show that tcasp8−/− mice develop an age-dependent lethal lymphoproliferative and lymphoinfiltrative immune disorder characterized by lymphoadenopathy, splenomegaly, and accumulation of T cell infiltrates in the lungs, liver, and kidneys. Peripheral casp8−/− T cells manifest activation marker up-regulation and are proliferating in the absence of any infection or stimulation. We also provide evidence suggesting that this immune disorder is different from the autoimmune lymphoproliferative syndrome. Interestingly, the condition described in tcasp8−/− mice manifests features consistent with the disorder described in humans with Caspase-8 deficiency. These findings suggest that tcasp8−/− mice may serve as an animal model to evaluate Caspase-8–deficient patient prognosis and therapy. Overall, our study uncovers novel in vivo functions for caspase-8 in immune regulation.

scholarly journals Restoration of motor innervation by the «end-to-side» neurorraphia: experimental modeling and clinical and instrumental control of reinnervation

2020 ◽  
Vol 13 (1) ◽  
pp. 24-33
Author(s):  
Aleksey Yur’evich Nisht ◽  
Nikolay Fedorovich Fomin ◽  
Artur Ilgizjvich Imelbaev ◽  
Anastasia Arturovna Mikulich
Keyword(s):  
Peripheral Nerve ◽  
Functional State ◽  
Peripheral Nerves ◽  
Peroneal Nerve ◽  
Common Peroneal Nerve ◽  
Distal Portion ◽  
Laboratory Animals ◽  
The Common ◽  
Reconstructive Plastic

The high probability of permanent loss of professional fitness and a significant risk of disability of the injured as a result of limb injuries with peripheral nerve damage contribute to both the continuous improvement of surgical techniques on the peripheral nerves, and the implementation of experimental and anatomical studies aimed at developing new ways to restore the lost innervation. Various types of peripheral nerve injuries are observed in peace and wartime victims in 2-6% and 9.8% of cases, respectively. The high degree of disability of patients with the consequences of peripheral nerve injuries requires improvement of diagnostic and reconstructive plastic approaches in this category of patients. A promising method of restoration of the distal part of the crossed nerve with extensive defects of the nerve trunk is its connection with the lateral surface of the intact donor nerve by the end-to-side neurorraphia. The lack of unambiguous views on the nature of reinnervation in this case, even in the presence of single publications on the positive outcomes of such interventions allow us to use this method only in the absence of the possibility of using autonerval transplants to replace extensive defects of peripheral nerves. The purpose of the study: in experiments on laboratory animals to determine the features of modeling trauma of nerve trunks in relation to the development of the main stages of recovery of lost innervation by connecting peripheral nerves by the end-to-side neurorraphia and to determine the range of simple and demonstrative methods of clinical and instrumental control of the functional state of the restored peripheral nerves in a long-term experiment on laboratory animals. Methods. A comprehensive experimental surgical and clinical-instrumental study was performed on 61 laboratory animals (Chinchilla rabbits of both sexes, phenotypically healthy individuals). In the experimental operating room under intravenous anesthesia, modeling of peripheral nerve defect was performed by resection of the total peroneal nerve with a length of 1 cm at the level of the middle third of the thigh. In animals of the studied group (n=39) to restore innervation, the "end-to-side" neurorraphia of the distal portion of the crossed common peroneal nerve with a specially formed defect of the perineural membrane on the lateral surface of the tibial nerve was performed. In the comparison group (n=22) no replacement of the defect of the common peroneal nerve was performed. The follow-up period after experimental interventions ranged from 1 to 290 days. Morphofunctional state of restored nerve trunks was determined by clinical, radiological and electrophysiological methods. Research results. Performing unilateral resections of the common peroneal nerve in laboratory animals (rabbits) with subsequent restoration of the distal portion of the crossed nerve by connecting it by the end-to-side neurorraphia with a nearby intact donor nerve allows to obtain reproducible in the experiment positive results of tissue reinnervation. Indirect assessment of the functional state of the restored nerves is possible using simple and accessible clinical tests, for example, the amplitude of the abduction of the toes of experimental animals in the study of the unconditional reflex of preparation for landing characterizes the conductivity of the common peroneal nerve. When performing experimental studies with multi-stage reconstructive plastic interventions on the peripheral nerves of laboratory animals, the inclusion of radiological methods in the complex of diagnostic measures allows performing in vivo visualization of the surgical intervention area, the restored nerve trunk, as well as the tissues innervated by its branches, which makes it possible to adjust the plan of subsequent morphological studies. Conclusions Performing resection of the common peroneal nerve of laboratory animals (rabbits) at the level of the middle third of the femur as a model of peripheral nerve injury allows to practice the technique of restoration of the distal section of the crossed nerve by connecting it with the adjacent intact donor nerve of the end-to-side neurorraphia. Performing a simple test with the initiation of an unconditional reflex of preparation for landing allows us to qualitatively assess the functional state of the common peroneal nerve in experimental animals. 3. The inclusion of radiological research methods in the program of comprehensive assessment of the peripheral nerves allows to perform their visualization in vivo with the definition of the main morphological characteristics of the restored in experimental reconstructive plastic interventions of nerve trunks.

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