Improving peripheral nerve regeneration: From molecular mechanisms to potential therapeutic targets

Chan, K. Ming; Gordon, Tessa; Zochodne, Douglas W.; Power, Hollie A.

doi:10.1016/j.expneurol.2014.09.006

Cited by 163 publications

(107 citation statements)

References 122 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Finally, there are several other surgical and pharmacological strategies that are being explored to promote regeneration and to counteract the negative effects of chronic nerve injuries [126]. These include the placement of end-to-side or side-toside nerve autografts between a donor nerve and a recipient denervated distal nerve stump [14,127], and the localized administration of FK506 and neurotrophic factors to the surgical site [11].…”

Section: Discussionmentioning

confidence: 99%

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

2016

Self Cite

View full text Add to dashboard Cite

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

show abstract

Section: Discussionmentioning

confidence: 99%

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, as mentioned earlier, neurotrophic and growth factors have demonstrated potential in enhancing nerve repair and regeneration by reducing neuronal death and promoting axonal outgrowth. Recent advances in molecular biology have indicated that targeting specific steps in molecular pathways may allow for purposeful pharmacologic intervention, potentially leading to a better functional recovery after nerve injury [63,280]. Major molecular pathways implicated in neuron survival and neurite outgrowth include PI3K (phosphatidylinositol-3 kinase)/Akt (protein kinase B)-signalling cascade, Ras-ERK (rat sarcoma-extracellular signalregulated kinase) pathway, the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and Rho-ROK signalling [280].…”

Section: Pharmacological Agentsmentioning

confidence: 99%

“…Recent advances in molecular biology have indicated that targeting specific steps in molecular pathways may allow for purposeful pharmacologic intervention, potentially leading to a better functional recovery after nerve injury [63,280]. Major molecular pathways implicated in neuron survival and neurite outgrowth include PI3K (phosphatidylinositol-3 kinase)/Akt (protein kinase B)-signalling cascade, Ras-ERK (rat sarcoma-extracellular signalregulated kinase) pathway, the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and Rho-ROK signalling [280]. PI3K/Akt cascade seems to provide trophic support for neurons, block apoptosis, facilitate signal transmission and mediate cell growth and differentiation in neurons.…”

Section: Pharmacological Agentsmentioning

confidence: 99%

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Pedrosa¹,

Caseiro²,

Santos³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

View full text Add to dashboard Cite

Human adult peripheral nerve injuries are a high incidence clinical problem that greatly affects patients' quality of life. Although peripheral nervous system has intrinsic regenerative capacity, this occurs in an incomplete or poorly functional manner. When a nerve fiber loses its continuity with consequent damage of the basal lamina tubes, axon spontaneous regeneration is disorganized and mismatched. These phenomena translate in an inadequate nerve functional recovery and consequent musculoskeletal incapacity. Nerve grafts still remain the gold standard in peripheral injuries treatment. However, this approach contains its disadvantages such as the necessity of primary surgery to harvest the autografts, loss of a functional nerve, donor site morbidity and longer surgery procedures. Therefore, biomaterials and tissue engineering can provide efficient resources and alternatives to nerve injury repair not only by the development of biocompatible structures but also, introducing neurotrophic factors and cellular systems to stimulate optimum clinical outcome. In this chapter, a comprehensive state-of-the art picture of tissue-engineered nerve grafts scaffolds, their application in nerve regeneration along with latest advances in peripheral nerve repair and future perspectives will be discussed, including our own large experience in this field of knowledge.

show abstract

“…Gene transcription, neural progenitor cells and nerve remodeling are dynamically regulated and induced in the regeneration cycle and in response to growth factors and respective signaling pathways, such as phosphatidylinositol-3 kinase (PI3K)-Akt and Ras/extracellular signal-regulated kinase, that are required for neurite survival and outgrowth. 88 The whole process could not only directly enhance the regeneration of nerve fibers but also indirectly induce angiogenesis, myelin formation, and SC proliferation and differentiation, and even activate potential stem cell lines in the region of the implants.…”

Section: Hypothesis: Peripheral Nerve Regeneration After Extraction Umentioning

confidence: 99%

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

et al. 2017

View full text Add to dashboard Cite

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal mechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma (PRP) therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field. Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and (pre-)clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of injured peripheral nerves around dental implants is discussed.

show abstract

Improving peripheral nerve regeneration: From molecular mechanisms to potential therapeutic targets

Cited by 163 publications

References 122 publications

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Contact Info

Product

Resources

About