Effects of delayed re-innervation on the expression of c-erbB receptors by chronically denervated rat Schwann cells in vivo

Li, H.; Terenghi, Giorgio; Hall, Susan

doi:10.1002/(sici)1098-1136(199708)20:4<333::aid-glia6>3.0.co;2-6

Cited by 136 publications

(84 citation statements)

References 50 publications

(42 reference statements)

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“…These results are in accordance with a previous study (Li, Terenghi, & Hall, 1997) in which chronically denervated SC were missing ErbB2. It was proposed that the lack of ErbB2 renders SC chronically insensitive to axonal derived NRG1, so contributing to the failure of axonal regeneration through chronically denervated distal nerve stumps.…”

Section: Nrg1 Isoform Expression During Nerve Regenerationsupporting

confidence: 93%

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

Gambarotta

Fregnan

Gnavi

et al. 2013

International Review of Neurobiology

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Neuregulin 1 (NRG1) is a multifunctional and versatile protein: its numerous isoforms can signal in a paracrine, autocrine or juxtacrine manner, playing a fundamental role during the development of the peripheral nervous system and during the process of nerve repair, suggesting that the treatment with NRG1 could improve functional outcome following injury. Accordingly, the use of NRG1 in vivo has already yielded encouraging results.The aim of this review is to focus on the role played by the different NRG1 isoforms during peripheral nerve regeneration and remyelination and to identify good candidates to be used for the development of tissue engineered medical devices delivering NRG1, with the final goal to promote better nerve repair.

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Section: Nrg1 Isoform Expression During Nerve Regenerationsupporting

confidence: 93%

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

Gambarotta

Fregnan

Gnavi

et al. 2013

International Review of Neurobiology

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Section: The Expression Of Nrg1 Isoforms and Their Receptors Changes Fomentioning

confidence: 99%

“…Guertin and coworkers examined the levels of erbB2 activation immediately following sciatic nerve transection and found that there is also an acute and transient increase in the levels of phosphorylated erbB2 and erbB3 in the first hour following injury, which decreases again by 3 h postinjury [80]. In chronically denervated sciatic nerves, expression levels of erbB receptors are much decreased [81].From 3 days postinjury a sustained increase in erbB2 and erbB3 expression is seen, and activation of these receptors is indicated by enhanced phosphorylation of erbB2; this is the time at which SCs undergo injury-induced proliferation [79].The expression of NRG1 type III by peripheral neurons initially decreases following nerve injury and then increases as axons begin to re-inner vate their targets [77,82]. Similar results were found in a facial nerve transection model where neuronal NRG1 type III levels were significantly downregulated and did not recover until 14 days postinjury [83].…”

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confidence: 99%

The role of neuregulin-1 in the response to nerve injury

Fricker

Bennett

2011

Future Neurology

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Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development. In adulthood, NRG1 is dispensable for the maintenance of the myelin sheath; however, this factor is required for both axon regeneration and remyelination following nerve injury. The outcome of NRG1 signaling depends on interactions with other pathways within Schwann cells such as Notch, integrin and cAMP signaling. In certain circumstances, this signaling pathway may be maladaptive; for instance, direct binding of Mycobacterium leprae onto erbB2 receptors produces excessive activation and can actually promote demyelination. Attempts to modulate this pathway in order to promote nerve repair will therefore need to give consideration to the exact isoform used, as well as how it is processed and the context in which it is presented to the Schwann cell. Keywordsneuregulin-1; neuropathy; peripheral nerve injury; regeneration; remyelination; repair; Schwann cell Peripheral nerve injury causes significant morbidity and reduced quality of life as a consequence of weakness, sensory loss and neuropathic pain. In total, 6% of the elderly population suffer from peripheral neuropathy [1], which can be caused by metabolic diseases such as diabetes, inherited genetic disorders such as Charcot-Marie-Tooth disease, infectious and inflammatory disorders including Guillan-Barré syndrome and traumatic injury to the nerve (which alone effects up to 300,000 people in Europe per year [1,2]). In contrast to the CNS, peripheral nerves have a significant regenerative capacity [3]; however, in patients, regeneration and the clinical outcome are often poor. Axons regenerate at a rate of approximately 1 mm per day, depending on the site of the lesion. There may be a delay of months if not years before the target zone is re-innervated, and by this time, the target organ and supporting cells may have irreversibly changed, becoming much less receptive to reinnervation. The current approaches to peripheral nerve repair following nerve transection are either to surgically suture the nerve or to bridge the gap between the two cut ends. Financial & competing interests disclosureThe authors have no other rel evant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Europe PMC Funders Group NRGs & the PNSNRGs Neuregulins are a family of growth factors en...

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“…Interestingly, the deterioration of the capacity of Schwann cells to support axonal regeneration after 4 weeks coincides with the decline in the number of infiltrated macrophages and the completion of Wallerian degeneration. 22,27,28 Likewise, the expression of the markers of the growth-promoting, nonmyelinating phenotype of Schwann cells declines after 4 weeks. 20 Thus, it appears that Schwann cells can maintain their growth-supportive phenotype only in the presence of active Wallerian degeneration.…”

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confidence: 99%

“…20 Thus, it appears that Schwann cells can maintain their growth-supportive phenotype only in the presence of active Wallerian degeneration. 12,28 Macrophages' key roles in Wallerian degeneration include removing debris 3 and producing cytokines that stimulate production of neurotrophic factors by nonneuronal cells of the distal nerve stumps, 8,10,12,21 including transforming growth factor-b (TGF-b). After nerve injury, TGF-b is secreted into the injured nerves by invading macrophages 2 and by Schwann cells themselves.…”

mentioning

confidence: 99%

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

Sulaiman¹,

Dreesen

2014

JNS

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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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Effects of delayed re-innervation on the expression of c-erbB receptors by chronically denervated rat Schwann cells in vivo

Cited by 136 publications

References 50 publications

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

The role of neuregulin-1 in the response to nerve injury

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

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