scholarly journals Robo2 drives target selective peripheral nerve regeneration in response to glia derived signals

2020 ◽  
Author(s):  
Patricia L. Murphy ◽  
Jesse Isaacman-Beck ◽  
Michael Granato
Keyword(s):  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Peripheral Nerve Regeneration ◽  
Choice Point ◽  
Branch Points ◽  
Nerve Branch ◽  
Dorsal Branch ◽  
Motor Nerves ◽  
Functional Regeneration ◽  
Selective Regeneration

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Zebrafish motor nerves are composed of a ventral and a dorsal branch that diverge at a choice point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify Robo2 as a key regulator of target selective regeneration. We demonstrate that Robo2 function in regenerating axons is required and sufficient to drive target selective regeneration, and that Robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined our results reveal a glia derived mechanism that acts locally via axonal Robo2 to promote target selective regeneration.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

Abstract TP473: Investigating the Pathogenesis of Moyamoya Disease Using Patient Derived Induced Pluripotent Stem Cells

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shailaja Rao ◽  
Qian Zhang ◽  
Haruto Uchino ◽  
Arjun Pendharkar ◽  
Michelle Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Moyamoya Disease ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Brdu Incorporation ◽  
Branch Points ◽  
Scratch Assay ◽  
Induced Pluripotent

Background: Moyamoya disease (MMD) is a rare, progressive steno-occlusive cerebrovascular disorder of the internal carotid artery, leading to stroke. Affected arteries exhibit thickened intima with depleted elastic lamina and media, indicating a dysfunction of the vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). However the pathogenesis of the disease is still unclear. We aim to address this gap in knowledge by using patient derived induced pluripotent stem cells (iPSCs), to generate VSMCs and ECs. Methods: Peripheral blood mononuclear cells (PBMCs) from controls and MMD patients (n=3 per group) were used for generating iPSCs. VSMC functionality was measured by collagen gel contraction assay and scratch assay. EC proliferative function was assessed by BrDU incorporation assay, and its migration capacity was evaluated by scratch assay and in vitro tube formation. VSMCs and ECs were also exposed to either hydrogen peroxide (H2O2) or normoxia/ hypoxia model (1%O 2 ) to investigate how cells respond to these insults. Hypoxia inducible factor 1α (HIF1α) activation was determined using western blot. Results: MMD VSMCs trended towards being more contractile and migrating faster than control VSMCs, in response to 10%FBS or SDF1α. On the other hand, MMD ECs migrated slower than control ECs in response to 10%FBS (p=0.0081) or VEGF (p=0.0072). MMD ECs also formed lesser tubes and exhibited fewer branch points when compared to controls. The rate of EC proliferation was similar between both groups. Cell death assays indicate that MMD VSMCs and ECs were more sensitive to the deleterious effects of H2O2 exposure when compared to control cells. Interestingly, MMD VSMCs had elevated HIF1α protein expression in normoxia, which was further increased after hypoxia. Conclusions: Our preliminary results indicate that both MMD VSMCs and ECs are dysfunctional and may be related to the elevated basal expression of HIF1α, possibly contributing to MMD pathology. We are currently investigating the interactions between VSMCs and ECs in MMD compared with controls using co-cultures. Ongoing studies also include transcriptome analysis of these differentiated cells, which will advance the understanding of the cellular and molecular mechanisms underlying MMD.

ELECTRODIAGNOSIS OF NEUROMUSCULAR DISEASE

PEDIATRICS ◽  
1964 ◽  
Vol 34 (5) ◽  
pp. 599-600
Author(s):  
EDWARD H. LAMBERT
Keyword(s):  
Conduction Velocity ◽  
Peripheral Nerves ◽  
Neuromuscular Disease ◽  
Clinical Neurophysiology ◽  
Clinical Investigation ◽  
Neuromuscular Disorders ◽  
Simple Method ◽  
The Past ◽  
Objective Evidence ◽  
Motor Nerves

THE past decade has seen a number of the techniques of clinical neurophysiology come into common use in the diagnosis of neuromuscular disease. One of these is the measurement of conduction velocity of motor nerves. Conduction velocity of nerves was only of academic interest until 1948 when a simple method for making reliable measurements in man was described and proved useful as a test of nerve function. It is now a frequent subject of clinical investigation and in many laboratories measurement of conduction velocity has become a routine diagnostic procedure. A review and extension of this work by Dunn and his associates, published in this issue of Pediatrics, emphasizes the importance of such measurements to pediatrics wherein objective evidence of functional impairment of nerves is of particular importance because the clinical examination may be so unsatisfactory. Conduction velocity of peripheral nerves, measurable quickly and simply, should be standard practice in the study of neuromuscular disorders in infants and children.

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.

scholarly journals THE LOCALIZED ACTION ON THE SPINAL CORD OF INTRAMUSCULARLY INJECTED TETANUS TOXIN

1942 ◽  
Vol 75 (5) ◽  
pp. 465-480 ◽  
Author(s):  
George H. Acheson ◽  
Oscar D. Ratnoff ◽  
Emanuel B. Schoenbach
Keyword(s):  
Spinal Cord ◽  
Tetanus Toxin ◽  
Peripheral Nerves ◽  
Mechanical Response ◽  
Motor Nerve ◽  
Single Stimulus ◽  
Altered State ◽  
Local Tetanus ◽  
Reflex Arc ◽  
Motor Nerves

Local tetanus limited to one leg was studied in cats after intramuscular injection of tetanus toxin. 1. The electric and mechanical response of the affected muscle after a single stimulus to the intact sensory-motor nerve is greater in amplitude and duration than the response of the corresponding muscle of the unaffected leg (Fig. 1). 2. This augmented response of the muscle is associated with an augmented response arising from the ipsilateral portion of the spinal cord, while the contralateral part of the cord is unaffected, as demonstrated by electrographic records from the motor nerves (Figs. 2 to 5). 3. The augmented muscular response is abolished when the reflex arc is broken, but the augmented response in the spinal cord is independent of changes in the muscle, the neuromuscular junction, the afferent and efferent peripheral nerves, and the dorsal root ganglia. 4. The augmented spinal response develops in the absence of the peripheral signs of local tetanus. Hence the pathogenesis of the altered state in the spinal cord is independent of the peripheral effects of the toxin. 5. In local tetanus, therefore, the toxin injected intramuscularly acts selectively upon the segments of the spinal cord which supply the innervation of the injected area. 6. The augmented spinal response may be prevented by section of the nerve trunks supplying the area of injection prior to the injection of the toxin. 7. It is concluded that in local tetanus the toxin is carried to the spinal cord by way of peripheral nerves.

Effect of Acupuncture Stimulation on Peripheral Nerve Regeneration Using Silicone Rubber Chambers

2001 ◽  
Vol 29 (03n04) ◽  
pp. 377-385 ◽  
Author(s):  
Yueh-Sheng Chen ◽  
Chun-Hsu Yao ◽  
Ter-Hsin Chen ◽  
Jaung-Geng Lin ◽  
Ching-Liang Hsieh ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Silicone Rubber ◽  
Peripheral Nerves ◽  
Acupuncture Treatment ◽  
Peripheral Nerve Regeneration ◽  
Promoting Effect ◽  
Positive Effects ◽  
Vessel Area ◽  
Axon Density ◽  
Growth Promoting

The purpose of this study was to determine whether acupuncture could affect the regeneration of a 10-mn gap of rat sciatic nerve created between the proximal and distal nerve stumps, which were sutured into silicone rubber tubes. Empty silicone rubber tubes with no further treatment were used as controls. Six weeks after implantation, the animals received the acupuncture or the electroneedling treatment exhibited a more mature ultrastructural nerve organization with significantly higher numbers in the axon density, the blood vessel area, and the percentage of blood vessel area occupied in total nerve area than the controls. In addition, the electroneedling could combine both the needling and the electrical stimulation to potentiate the nerve-growth promoting effect of the acupuncture treatment. These results showed that acupuncture treatment could elicit positive effects on regenerated peripheral nerves.

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.

scholarly journals Lymphatic Muscle Cells Contribute to Dysfunction of the Synovial Lymphatic System in Inflammatory Arthritis in Mice

2020 ◽  
Author(s):  
Qianqian Liang ◽  
Li Zhang ◽  
Hao Xu ◽  
Jinlong Li ◽  
Yan Chen ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Panax Notoginseng ◽  
Muscle Cells ◽  
Lv Function ◽  
No Production ◽  
Branch Points ◽  
Hind Limbs ◽  
And Function

Abstract Background. We previous studies reveal impaired draining function of the synovial lymphatic vessel (LV) contributes to inflammatory arthritis, but the cellular and molecular mechanisms involved are not fully understood.Objective. To investigate the involvement of lymphatic muscle cells (LMCs) in mediating impaired LV function in inflammatory arthritis.Methods. TNF transgenic (TNF-Tg) arthritic mice were used. Structure and function of the LVs that drain the hind limbs were examined by whole-mount immunofluorescence staining, electron microscope, and near-infrared lymphatic imaging. Primary LMCs were treated with TNF, and the changes in proliferation, apoptosis, and functional gene expression were assessed. Roles of the herbal drug, Panax Notoginseng Saponins (PNS), in arthritis and LVs were studied.Results. TNF-Tg mice developed ankle arthritis with age, which was associated with abnormalities of LVs: 1) dilated capillary LVs with few branch points; 2) mature LVs with reduced LMC coverage and draining function; 3) degenerative and apoptotic appearance of LMCs. TNF caused LMC apoptosis, reduced expression of muscle functional genes, and promoted the production of nitric oxide (NO) by lymphatic endothelial cells (LECs). PNS attenuated arthritis, restored LMC coverage and draining function of mature LVs, inhibited TNF-mediated NO expression, and reduced LMC apoptosis.Conclusion. The impaired draining function of LVs in TNF-Tg mice involves LMC apoptosis. TNF promotes LMC death directly and indirectly via NO production by LECs. PNS attenuates arthritis, improves LVs, and prevents TNF-induced LMC apoptosis by inhibiting NO production of LECs. LMCs contribute to the dysfunction of synovial LVs in inflammatory arthritis.

scholarly journals Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice

2021 ◽  
Author(s):  
Qianqian Liang ◽  
Li Zhang ◽  
Hao Xu ◽  
Jinlong Li ◽  
Yan Chen ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Panax Notoginseng ◽  
Muscle Cells ◽  
Lv Function ◽  
No Production ◽  
Branch Points ◽  
Hind Limbs ◽  
And Function

Abstract Background. Our previous studies reveal that impaired draining function of the synovial lymphatic vessel (LV) contributes to the pathogenesis of inflammatory arthritis, but the cellular and molecular mechanisms involved are not fully understood.Objective. To investigate the involvement of lymphatic muscle cells (LMCs) in mediating impaired LV function in inflammatory arthritis. Methods. TNF transgenic (TNF-Tg) arthritic mice were used. Structure and function of the LVs that drained the hind limbs were examined by whole-mount immunofluorescence staining, electron microscopy, and near-infrared lymphatic imaging. Primary LMCs were treated with TNF, and the changes in proliferation, apoptosis, and functional gene expression were assessed. The roles of the herbal drug, Panax Notoginseng Saponins (PNS), in arthritis and LVs were studied.Results. TNF-Tg mice developed ankle arthritis with age, which was associated with abnormalities of LVs: 1) dilated capillary LVs with few branch points; 2) mature LVs with reduced LMC coverage and draining function; 3) degenerative and apoptotic appearance of LMCs. TNF caused LMC apoptosis, reduced expression of muscle functional genes, and promoted the production of nitric oxide (NO) by lymphatic endothelial cells (LECs). PNS attenuated arthritis, restored LMC coverage and draining function of mature LVs, inhibited TNF-mediated NO expression, and reduced LMC apoptosis. Conclusion. The impaired draining function of LVs in TNF-Tg mice involves LMC apoptosis. TNF promotes LMC death directly and indirectly via NO production by LECs. PNS attenuates arthritis, improves LVs, and prevents TNF-induced LMC apoptosis by inhibiting NO production of LECs. LMCs contribute to the dysfunction of synovial LVs in inflammatory arthritis.

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