Electrical stimulation for peripheral nerve injury treatment

Electrical stimulation for peripheral nerve injury treatment

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system’s intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option 1).


Electrical stimulation is regarded pivotal to promote repair of nerve injury, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche.

Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment 2).


Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings 3).


Zhang et al. demonstrated a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution 4).


The frequency of stimulation is an important factor in the success of both quality and quantity of axon regeneration as well as growth of the surrounding myelin and blood vessels that support the axon. Histological analysis and measurement of regeneration showed that low frequency stimulation had a more successful outcome than high frequency stimulation on regeneration of damaged sciatic nerves.

The use of autologous nerve grafting procedures that involve redirection of regenerative donor nerve fibers into the graft conduit has been successful in restoring target muscle function. Localized delivery of soluble neurotrophic factors may help promote the rate of axon regeneration observed within these graft conduits.

An expanding area of nerve regeneration research deals with the development of scaffolding and bio-conduits. Scaffolding developed from biomaterial would be useful in nerve regeneration if they successfully exhibit essentially the same role as the endoneurial tubes and Schwann cell do in guiding regrowing axons.

The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them. In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in nonneuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival, and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point toward the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury 5).


1)

Willand MP, Nguyen MA, Borschel GH, Gordon T. Electrical Stimulation to Promote Peripheral Nerve Regeneration. Neurorehabil Neural Repair. 2016 Jun;30(5):490-6. doi: 10.1177/1545968315604399. Epub 2015 Sep 10. PMID: 26359343.
2)

Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020 Oct;332:113397. doi: 10.1016/j.expneurol.2020.113397. Epub 2020 Jul 3. PMID: 32628968.
3)

MacEwan MR, Gamble P, Stephen M, Ray WZ. Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators. J Neurosurg. 2018 Feb 9:1-10. doi: 10.3171/2017.8.JNS163020. Epub ahead of print. PMID: 29424647.
4)

Zhang Y, Chen S, Xiao Z, Liu X, Wu C, Wu K, Liu A, Wei D, Sun J, Zhou L, Fan H. Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration. Adv Healthc Mater. 2021 Jun 27:e2100695. doi: 10.1002/adhm.202100695. Epub ahead of print. PMID: 34176235.
5)

Dahlin LB. The role of timing in nerve reconstruction. Int Rev Neurobiol. 2013;109:151-64. doi: 10.1016/B978-0-12-420045-6.00007-9. Review. PubMed PMID: 24093611.

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