scholarly journals RalGTPases contribute to Schwann cell repair after nerve injury via regulation of process formation

2019 ◽  
Vol 218 (7) ◽  
pp. 2370-2387 ◽  
Author(s):  
Jorge Galino ◽  
Ilaria Cervellini ◽  
Ning Zhu ◽  
Nina Stöberl ◽  
Meike Hütte ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Small Gtpases ◽  
Membrane Dynamics ◽  
Process Formation ◽  
Ral Gtpases ◽  
Injury And Repair ◽  
Recovery Of Motor Function

RalA and RalB are small GTPases that are involved in cell migration and membrane dynamics. We used transgenic mice in which one or both GTPases were genetically ablated to investigate the role of RalGTPases in the Schwann cell (SC) response to nerve injury and repair. RalGTPases were dispensable for SC function in the naive uninjured state. Ablation of both RalA and RalB (but not individually) in SCs resulted in impaired axon remyelination and target reinnervation following nerve injury, which resulted in slowed recovery of motor function. Ral GTPases were localized to the leading lamellipodia in SCs and were required for the formation and extension of both axial and radial processes of SCs. These effects were dependent on interaction with the exocyst complex and impacted on the rate of SC migration and myelination. Our results show that RalGTPases are required for efficient nerve repair by regulating SC process formation, migration, and myelination, therefore uncovering a novel role for these GTPases.

Misdirection and guidance of regenerating axons after experimental nerve injury and repair

2014 ◽  
Vol 120 (2) ◽  
pp. 493-501 ◽  
Author(s):  
Godard C. W. de Ruiter ◽  
Robert J. Spinner ◽  
Joost Verhaagen ◽  
Martijn J. A. Malessy
Keyword(s):  
Nerve Injury ◽  
Nerve Repair ◽  
Sensory Nerve ◽  
Retrograde Tracing ◽  
Sensory Axons ◽  
Motor Nerves ◽  
Tracing Techniques ◽  
Injury And Repair ◽  
New Strategies

Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin, and vice versa—that is, sensory axons projecting toward muscle. In the repair of motor nerves innervating different distal targets, misdirection may result in reinnervation of the wrong target muscle, which might function antagonistically. In sensory nerve repair, misdirection might give an increased perceptual territory. After median nerve repair, for example, this might lead to a dysfunctional hand. Different factors may be involved in the misdirection of regenerating axons, and there may be various mechanisms that can later correct for misdirection. In this review the authors discuss these different factors and mechanisms that act along the pathway of the regenerating axon. The authors review recently developed evaluation methods that can be used to investigate the accuracy of regeneration after nerve injury and repair (including the use of transgenic fluorescent mice, retrograde tracing techniques, and motion analysis). In addition, the authors discuss new strategies that can improve in vivo guidance of regenerating axons (including physical guidance with multichannel nerve tubes and biological guidance accomplished using gene therapy).

An overture to basic science aspects of nerve injuries

2011 ◽  
Vol 36 (9) ◽  
pp. 726-729 ◽  
Author(s):  
T. Carlstedt
Keyword(s):  
Nervous System ◽  
Surgical Treatment ◽  
Molecular Biology ◽  
Nerve Injury ◽  
Basic Science ◽  
Nerve Repair ◽  
Functional Improvement ◽  
New Concepts ◽  
Injury And Repair ◽  
Inhibitory Molecules

Does the lack of improvement in surgical treatment of nerve injury despite thousands of years of research disturb you? Do you think that basic science has not really contributed to any advancement in the treatment of nerve injury? Have you contributed? Do you think that new molecular biology knowledge in nerve injury and repair is important? Knowing from basic science that the immature nervous system is more fragile would you agree with the view that to be ‘aggressive’ in surgery of the newborn with a brachial plexus injury could be unscrupulous? As molecular biology of the nervous system has demonstrated that the best conditions for regeneration occur immediately after an injury do you find the approach of postponing surgery until at least 3 months after a closed nerve injury to be ignorant and even negligent? Taking into account the normal occurrence of inhibitory molecules in the uninjured peripheral nerve do you think that functional improvement from end to side nerve repair is a myth? Are the recent attempts to artificially enhance nerve regeneration for instance in synthetical conduits like nature seen ‘through a glass darkly’? Do you agree that new concepts in surgical treatment of nerve injury are timely? Do you have the time?

The hypoglossal–facial nerve repair as a method to improve recovery of motor function after facial nerve injury

2011 ◽  
Vol 193 (4) ◽  
pp. 304-313 ◽  
Author(s):  
Umut Ozsoy ◽  
Arzu Hizay ◽  
Bahadir Murat Demirel ◽  
Ozlem Ozsoy ◽  
Sureyya Bilmen Sarikcioglu ◽  
...  
Keyword(s):  
Facial Nerve ◽  
Nerve Injury ◽  
Motor Function ◽  
Nerve Repair ◽  
Facial Nerve Injury ◽  
Recovery Of Motor Function

A need to clarify the role of apolipoprotein E in peripheral nerve injury and repair

2005 ◽  
Vol 10 (3) ◽  
pp. 344-345 ◽  
Author(s):  
Fatemeh Geranmayeh ◽  
Lynne Christian ◽  
Federico E. Turkheimer ◽  
Stephen M. Gentleman ◽  
Kevin S. O'Neill
Keyword(s):  
Peripheral Nerve ◽  
Apolipoprotein E ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Injury And Repair

scholarly journals Obligatory role of Schwann cell‐specific erythropoietin receptors in erythropoietin‐induced functional recovery and neurogenic muscle atrophy after nerve injury

2020 ◽  
Author(s):  
M A Hassan Talukder ◽  
Jung Il Lee ◽  
John P. Hegarty ◽  
Anagha A. Gurjar ◽  
Mary O'Brien ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Nerve Injury ◽  
Muscle Atrophy ◽  
Functional Recovery

Exosomes as a promising therapeutic strategy for peripheral nerve injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Tianhao Yu ◽  
Yingxi Xu ◽  
Muhammad Arslan Ahmad ◽  
Rabia Javed ◽  
Haruo Hagiwara ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Repair ◽  
Nerve Grafts ◽  
Axonal Regrowth ◽  
Vascular Regeneration

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives of autologous nerve grafts, and a variety of cells and neurotrophic factors were introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repair capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair. Keywords: Exosome, nerve regeneration, peripheral nerve injury, Schwann cell, axonal regrowth, inflammation, vascular regeneration.

scholarly journals Role of Rho-GTPases in complement-mediated glomerular epithelial cell injury

2007 ◽  
Vol 293 (1) ◽  
pp. F148-F156 ◽  
Author(s):  
Hui Zhang ◽  
Andrey V. Cybulsky ◽  
Lamine Aoudjit ◽  
Jianxin Zhu ◽  
Hongping Li ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Cell Injury ◽  
Rho Gtpase ◽  
Morphological Changes ◽  
Small Gtpases ◽  
Dominant Negative ◽  
Glomerular Epithelial Cell ◽  
Rhoa Activity ◽  
Process Formation

Visceral glomerular epithelial cells (GEC) are essential for maintenance of normal glomerular permselectivity. The actin cytoskeleton is a key determinant of GEC morphology and function. In the rat passive Heymann nephritis (PHN) model of membranous nephropathy, complement C5b-9 induces nonlytic GEC injury associated with morphological changes of GEC and proteinuria. The current study addresses the role of Rho family of small GTPases in complement-mediated GEC injury. When cultured rat GEC were stimulated with complement C5b-9 for 18 h, RhoA activity increased, whereas Rac1/Cdc42 activities decreased, compared with control cells. Similar changes in Rho-GTPase activities were observed in glomeruli from rats with PHN. The amount of active p190RhoGAP, a negative upstream regulator of RhoA, was decreased in complement-stimulated GEC, potentially contributing to increased RhoA activity. To address the functional effects of Rho-GTPases, GEC were transfected with constitutively active (CA) or dominant negative (DN) Rho-GTPase mutants. GEC transfected with CA-RhoA showed a smaller and round contour and prominent cortical F-actin. In contrast, GEC transfected with CA-Rac1 demonstrated morphological changes that resembled process formation. In addition, expression of CA-RhoA attenuated complement-mediated cytotoxicity, whereas cytotoxicity was augmented by DN-RhoA. Thus exposure of GEC to complement alters the balance of RhoA, Rac1, and Cdc42 activities. The activity of Rac1 may contribute to process formation, while activation of RhoA (e.g., in the setting of complement attack), with or without blunting of Rac1 activity, may have an opposite effect, i.e., contribute to foot process effacement. Activation of RhoA increases the resistance of GEC to complement-mediated injury.

scholarly journals Ral GTPases in Schwann cells promote radial axonal sorting in the peripheral nervous system

2019 ◽  
Vol 218 (7) ◽  
pp. 2350-2369 ◽  
Author(s):  
Andrea Ommer ◽  
Gianluca Figlia ◽  
Jorge A. Pereira ◽  
Anna Lena Datwyler ◽  
Joanne Gerber ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Cell Biology ◽  
Physiological Role ◽  
Small Gtpases ◽  
Cell Process ◽  
Peripheral Nerve Sheath Tumors ◽  
Ral Gtpases ◽  
Radial Sorting

Small GTPases of the Rho and Ras families are important regulators of Schwann cell biology. The Ras-like GTPases RalA and RalB act downstream of Ras in malignant peripheral nerve sheath tumors. However, the physiological role of Ral proteins in Schwann cell development is unknown. Using transgenic mice with ablation of one or both Ral genes, we report that Ral GTPases are crucial for axonal radial sorting. While lack of only one Ral GTPase was dispensable for early peripheral nerve development, ablation of both RalA and RalB resulted in persistent radial sorting defects, associated with hallmarks of deficits in Schwann cell process formation and maintenance. In agreement, ex vivo–cultured Ral-deficient Schwann cells were impaired in process extension and the formation of lamellipodia. Our data indicate further that RalA contributes to Schwann cell process extensions through the exocyst complex, a known effector of Ral GTPases, consistent with an exocyst-mediated function of Ral GTPases in Schwann cells.

scholarly journals Role of macrophages in peripheral nerve injury and repair

2019 ◽  
Vol 14 (8) ◽  
pp. 1335 ◽  
Author(s):  
Feng Chang ◽  
Yu Wang ◽  
Ping Liu ◽  
Jiang Peng ◽  
Gong-Hai Han ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Injury And Repair
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