Efficacy of glial growth factor and nerve growth factor on the recovery of traumatic facial paralysis

Yildiz, Mücahit; Karlıdağ, Turgut; Yalçin, Süleyman; Özoğul, Candan; Keleş, Erol; Alpay, Hayrettin Cengiz; Yanilmaz, Muhammed

doi:10.1007/s00405-011-1492-3

Cited by 20 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is indicated that exogenous treatment of NRG β1 would increase the length of regenerating axons and improve the functional outcome after sciatic nerve injury [32], [33]. Pharmacological report also documented that following facial nerve transection, NRG β1 could increase the Sc nuclei and reduce the myelin debris [34]. Our current study was thus in good agreements with these findings in which application of NRG β1 also showed an increase of migrated Sc and speeding the nerve regeneration following end-to-side neurorraphy (Figs.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

et al. 2013

View full text Add to dashboard Cite

BackgroundAdequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches.Methodology and Principal FindingsCultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles.ConclusionsAs neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The use of recombinant or virally expressed NRG1 therapeutically following peripheral nerve injury has shown some efficacy in promoting axon regeneration (Chen et al , 1998; Joung et al , 2010; Fricker and Bennett, 2011; Yildiz et al. , 2011).…”

Section: Discussionmentioning

confidence: 99%

Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination

Fricker

Antunes-Martins

Galino

et al. 2013

Brain

View full text Add to dashboard Cite

Neuregulin 1 acts as an axonal signal that regulates multiple aspects of Schwann cell development including the survival and migration of Schwann cell precursors, the ensheathment of axons and subsequent elaboration of the myelin sheath. To examine the role of this factor in remyelination and repair following nerve injury, we ablated neuregulin 1 in the adult nervous system using a tamoxifen inducible Cre recombinase transgenic mouse system. The loss of neuregulin 1 impaired remyelination after nerve crush, but did not affect Schwann cell proliferation associated with Wallerian degeneration or axon regeneration or the clearance of myelin debris by macrophages. Myelination changes were most marked at 10 days after injury but still apparent at 2 months post-crush. Transcriptional analysis demonstrated reduced expression of myelin-related genes during nerve repair in animals lacking neuregulin 1. We also studied repair over a prolonged time course in a more severe injury model, sciatic nerve transection and reanastamosis. In the neuregulin 1 mutant mice, remyelination was again impaired 2 months after nerve transection and reanastamosis. However, by 3 months post-injury axons lacking neuregulin 1 were effectively remyelinated and virtually indistinguishable from control. Neuregulin 1 signalling is therefore an important factor in nerve repair regulating the rate of remyelination and functional recovery at early phases following injury. In contrast to development, however, the determination of myelination fate following nerve injury is not dependent on axonal neuregulin 1 expression. In the early phase following injury, axonal neuregulin 1 therefore promotes nerve repair, but at late stages other signalling pathways appear to compensate.

show abstract

“…Rats treated every 24 h for 4 days beginning 24 h after sciatic nerve injury with recombinant NRG1 type II showed improvement in measures of axon regeneration, including axon diameter and myelin thickness, assessed at 2 months postinjury, and had accelerated functional recovery as determined by the sciatic functional index (SFI) [92]. In addition, in rabbits with a facial nerve transection, treatment with NRG1 type II at the time of injury and 24 and 28 h postinjury resulted in an increase in SC nuclei and a reduction in myelin debris at 2 months postinjury [93]. Furthermore, rats injected intraneurally into both the proximal and distal stump of the sciatic nerve at the time of transection with an adenovirus expressing just the β-EGF domain of NRG1 type I increased the length of regenerating axons, expression of GAP43 at 3 weeks following injury and showed an improved functional outcome determined by gait ana lysis [94].…”

mentioning

confidence: 97%

The Role of Neuregulin-1 In the Response To Nerve Injury

Fricker

Bennett

2011

Future Neurol.

View full text Add to dashboard Cite

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...

show abstract

Efficacy of glial growth factor and nerve growth factor on the recovery of traumatic facial paralysis

Cited by 20 publications

References 19 publications

Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination

The Role of Neuregulin-1 In the Response To Nerve Injury

Contact Info

Product

Resources

About