Effects of PACAP on Schwann Cells: Focus on Nerve Injury

Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal regrowth and restoration of myelin sheaths on regenerating axons. Following nerve injury, Schwann cells respond adaptively to damage by acquiring a new phenotype. In particular, some of them localize in the distal stump to form the Bungner band, a regeneration track in the distal site of the injured nerve, whereas others produce cytokines involved in recruitment of macrophages infiltrating into the nerve damaged area for axonal and myelin debris clearance. Several neurotrophic factors, including pituitary adenylyl cyclase-activating peptide (PACAP), promote survival and axonal elongation of injured neurons. The present review summarizes the evidence existing in the literature demonstrating the autocrine and/or paracrine action exerted by PACAP to promote remyelination and ameliorate the peripheral nerve inflammatory response following nerve injury.

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Effect of local application of transforming growth factor–β at the nerve repair site following chronic axotomy and denervation on the expression of regeneration-associated genes

Journal of Neurosurgery ◽

10.3171/2014.4.jns131251 ◽

2014 ◽

Vol 121 (4) ◽

pp. 859-874 ◽

Cited By ~ 11

Author(s):

Wale Sulaiman ◽

Thomas D. Dreesen

Keyword(s):

Growth Factor ◽

Schwann Cells ◽

Nerve Injury ◽

Functional Recovery ◽

Transforming Growth Factor ◽

Nerve Repair ◽

Transforming Growth Factor Β ◽

Distal Stump ◽

Repair Site ◽

Gene And Protein Expression

Object Although peripheral nerves can regenerate after traumatic injury, functional recovery is often suboptimal, especially after injuries to large nerve trunks such as the sciatic nerve or brachial plexus. Current research with animal models suggests that the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets due to the loss of neurotrophic support by Schwann cells in the distal stump of injured nerves. This study was designed to investigate the effect of one-time application of transforming growth factor–β (TGF-β) at the repair site of chronically injured nerve. Methods The authors used the rat tibial nerve injury and repair model to investigate the effects of application of physiological concentrations of TGF-β plus forskolin or forskolin alone in vivo at the repair site on gene and protein expression and axon regeneration at 6 weeks after nerve repair. They used gene expression profiling and immunohistochemical analysis of indicative activated proteins in Schwann cells to evaluate the effects of treatments on the delayed repair. They also quantified the regenerated axons distal to the repair site by microscopy of paraffin sections. Results Both treatment with forskolin only and treatment with TGF-β plus forskolin resulted in increased numbers of axons regenerated compared with saline-only control. There was robust activation and proliferation of both Schwann cells and macrophages reminiscent of the processes during Wallerian degeneration. The treatment also induced upregulation of genes implicated in cellular activation and growth as detected by gene array. Conclusions Addition of TGF-β plus forskolin to the repair after chronic nerve injury improved axonal regeneration, probably via upregulation of required genes, expression of growth-associated protein, and reactivation of Schwann cells and macrophages. Further studies are required to better understand the mechanism of the positive effect of TGF-β treatment on old nerve injuries.

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Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury

BioMed Research International ◽

10.1155/2015/237507 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 70

Author(s):

Aikeremujiang Muheremu ◽

Qiang Ao

Keyword(s):

Stem Cells ◽

Clinical Practice ◽

Peripheral Nerve ◽

Schwann Cells ◽

Nerve Injury ◽

Neurotrophic Factors ◽

Peripheral Nerve Injury ◽

Functional Outcomes ◽

Nerve Conduits ◽

New Construction

With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. Nerve conduits range from biological tubes to synthetic tubes, and from nondegradable tubes to biodegradable tubes. Researchers have explored hollow tubes, tubes filled with scaffolds containing neurotrophic factors, and those seeded with Schwann cells or stem cells. The therapeutic effect of nerve conduits is improving with increasing choice of conduit material, new construction of conduits, and the inclusion of neurotrophic factors and support cells in the conduits. Improvements in functional outcomes are expected when these are optimized for use in clinical practice.

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Obestatin signaling controls Schwann cells and axonal transport to counteract neuromuscular synaptic loss in skeletal muscle

10.21203/rs.3.rs-55898/v1 ◽

2020 ◽

Author(s):

Jesus P Camiña ◽

Agustín Sánchez-Temprano ◽

Saúl Leal-López ◽

Jessica González-Sánchez ◽

Carlos S. Mosteiro ◽

...

Keyword(s):

Skeletal Muscle ◽

Peripheral Nerve ◽

Schwann Cells ◽

Nerve Injury ◽

Nerve Repair ◽

Axon Growth ◽

Neuromuscular Synapses ◽

Axonal Regrowth ◽

Peripheral Nerve System ◽

Nerve System

Abstract Background. Injuries to the peripheral nerve system are common conditions, with broad spectrum of symptoms depending on the impaired nerves and severity of damage. Although peripheral nervous system retains a remarkable ability for regeneration, it is estimated that less than ten percent of patients fully recover function after nerve injury and the available treatments remain suboptimal. Here, we identify a role for the obestatin/GPR39 system in the regulation of the Schwann cell plasticity as well as in the preservation of neuromuscular synapses in the course of nerve repair. Methods. Utilizing a compression model of sciatic nerve injury, axonotmesis, we assessed the obestatin-related regenerative response in the peripheral nerve system. The role of the obestatin/GPR39 system was further evaluated on immortalized rat Schwann cells, IFRS1, and the model of neuronal differentiation, PC12 cells. The interactions between SCs and neurons was evaluated using a co-culture system that combine the SC cell line IFRS1 and the NGF-primed PC12. Results. Obestatin signaling directs proliferation and migration of Schwann cells that sustain axonal regrowth and later remyelinate regenerated axons. We provide evidence supporting the preservation of skeletal muscle by the maintenance of neuromuscular synapses through the axonal regulation of calpain-calpastatin proteolytic system. This encompasses the control of skeletal muscle homeostasis by regulation of the ubiquitin proteasome system and the autophagy machinery. Conclusions. These results provide important insights into how the obestatin/GPR39 system promotes nerve repair through integration of multiple molecular cues of neuron-Schwann cells crosstalk aimed to promote axon growth and guide axons back to their targets.

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Schwann cells and trigeminal neuralgia

Molecular Pain ◽

10.1177/1744806920963809 ◽

2020 ◽

Vol 16 ◽

pp. 174480692096380

Author(s):

Jia-Yi Liao ◽

Tian-Hua Zhou ◽

Bao-Kang Chen ◽

Zeng-Xu Liu

Keyword(s):

Trigeminal Neuralgia ◽

Peripheral Nerve ◽

Schwann Cells ◽

Nerve Injury ◽

Trigeminal Nerve ◽

Myelin Sheath ◽

Neurotrophic Factors ◽

Future Research ◽

Research Directions ◽

Future Research Directions

Schwann cells are components of the peripheral nerve myelin sheath, which supports and nourishes axons. Upon injury of the trigeminal nerve, Schwann cells are activated and cause trigeminal neuralgia by engulfing the myelin sheath and secreting various neurotrophic factors. Further, Schwann cells can repair the damaged nerve and thus alleviate trigeminal neuralgia. Here, we briefly describe the development and activation of Schwann cells after nerve injury. Moreover, we expound on the occurrence, regulation, and treatment of trigeminal neuralgia; further, we point out the current research deficiencies and future research directions.

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Faculty Opinions recommendation of Terminal Schwann cells participate in neuromuscular synapse remodeling during reinnervation following nerve injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718370894.793494732 ◽

2014 ◽

Author(s):

Rhona Mirsky

Keyword(s):

Schwann Cells ◽

Nerve Injury ◽

Neuromuscular Synapse ◽

Terminal Schwann Cells

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Biology of the repair of central nervous system demyelinated lesions: an appraisal

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1996000200026 ◽

1996 ◽

Vol 54 (2) ◽

pp. 331-334 ◽

Cited By ~ 3

Author(s):

L. A. V Peireira ◽

M. A. Cruz-Höfling ◽

M. S. J. Dertkigil ◽

D. L. Graça

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Schwann Cells ◽

Demyelinating Disease ◽

Experimental Models ◽

Primitive Cell ◽

Marked Influence ◽

Myelin Sheaths ◽

Human Material ◽

The Central Nervous System

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

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Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

Journal of Neurosurgery ◽

10.3171/2013.4.jns121189 ◽

2013 ◽

Vol 119 (3) ◽

pp. 720-732 ◽

Cited By ~ 30

Author(s):

Yerko A. Berrocal ◽

Vania W. Almeida ◽

Ranjan Gupta ◽

Allan D. Levi

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Schwann Cells ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Fluorescent Protein ◽

Control Groups ◽

Myelinated Axons ◽

Segmental Nerve ◽

Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

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Effects of Nerve Injury and Colchicine Treatment on the Recovery of Non-Specific Cholinesterase Activity in Specialized Schwann Cells of Rat Simple Lamellar Corpuscles

Mechanoreceptors ◽

10.1007/978-1-4899-0812-4_57 ◽

1988 ◽

pp. 301-305 ◽

Cited By ~ 2

Author(s):

Petr Dubový ◽

Jan Hájek ◽

Ivana Svíženská ◽

Lubomír Malinovský ◽

Hana Procházková

Keyword(s):

Schwann Cells ◽

Nerve Injury ◽

Cholinesterase Activity ◽

Colchicine Treatment

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S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502008000600014 ◽

2008 ◽

Vol 23 (6) ◽

pp. 555-560 ◽

Cited By ~ 11

Author(s):

Tatiana Duobles ◽

Thais de Sousa Lima ◽

Beatriz de Freitas Azevedo Levy ◽

Gerson Chadi

Keyword(s):

Growth Factor ◽

Sciatic Nerve ◽

Fibroblast Growth Factor ◽

Schwann Cells ◽

Nerve Injury ◽

Satellite Cells ◽

Peripheral Nerves ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Cultured Schwann Cells

PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF) and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG). Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.

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