Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats

Elzinga, Kate; Tyreman, Neil; Ladak, Adil; Savaryn, Bohdan; Olson, Jaret; Gordon, Tessa

doi:10.1016/j.expneurol.2015.03.022

Cited by 119 publications

(104 citation statements)

References 66 publications

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“…This improvement was demonstrated in a number of published and ongoing studies of human nerve injuries [94,125,and Chan,unpublished data]. Importantly, the electrical stimulation regimen is effective after delayed nerve repair in animals and humans [5,94]. These very promising findings anticipate further studies that may form the basis for the adoption of technique of intraoperative brief electrical stimulation at the time of surgical repair of injured nerves to become the standard of practice in management of peripheral nerve injuries.…”

Section: Discussionmentioning

confidence: 90%

“…The study of Huang et al [92] indicated a very small but significant increase of~10 % and 3 % in the regeneration of axons by motor and sensory neurons, respectively, when the sciatic nerve was subjected to a 20-min period of low-frequency electrical stimulation after a delayed nerve repair via a 5-mm long hollow nerve conduit. Hence, the question of efficacy of the electrical stimulation on chronically injured nerves remained prior to our more recent study in which we again used a crosssuture technique to examine whether the brief 1-h 20-Hz electrical stimulation regimen could promote axon regeneration after chronic axotomy and/or chronic denervation [5]. Indeed, we found that the electrical stimulation was very effective in promoting outgrowth of axons from chronically axotomized motor and sensory neurons, from freshly axotomized motor and sensory neurons that regenerated axons into chronically denervated nerve stumps (compare Fig.…”

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

“…Only 2 studies [5,92] have addressed the important clinical and unanswered question of whether electrical stimulation is effective under conditions of the chronic axotomy and chronic denervation, conditions that human nerves suffer even after immediate nerve repair as a consequence of long distances between the site of nerve repair and denervated targets. The study of Huang et al [92] indicated a very small but significant increase of~10 % and 3 % in the regeneration of axons by motor and sensory neurons, respectively, when the sciatic nerve was subjected to a 20-min period of low-frequency electrical stimulation after a delayed nerve repair via a 5-mm long hollow nerve conduit.…”

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

“…5b and c with A), and from chronically axotomized motor and sensory neurons that regenerated their axons into chronically denervated nerve stumps (Fig. 5d), and, in turn, reinnervated their chronically denervated muscles [5].…”

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

“…The basis for this poor regeneration is explored in this review before presenting the evidence that brief electrical stimulation is effective in accelerating axon outgrowth across injury sites [3,4] that, even after delayed surgical repair of injured peripheral nerves, functional recovery is enhanced [5]. Associated with this enhancement, the electrical stimulation upregulates the expression of neurotrophic factors and, in turn, growth-associated genes [6,7].…”

Section: Introductionmentioning

confidence: 99%

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

2016

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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.

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Section: Discussionmentioning

confidence: 90%

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2016

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Human Organs‐on‐Chips: A Review of the State‐of‐the‐Art, Current Prospects, and Future Challenges

et al. 2021

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New emerging technologies, remarkably miniaturized 3D organ models and microfluidics, enable simulation of the real in vitro microenvironment ex vivo more closely. There are many fascinating features of innovative organ‐on‐a‐chip (OOC) technology, including the possibility of integrating semipermeable and/or stretchable membranes, creating continuous perfusion of fluids into microchannels and chambers (while maintaining laminar flow regime), embedding microdevices like microsensors, microstimulators, micro heaters, or different cell lines, along with other 3D cell culture technologies. OOC systems are designed to imitate the structure and function of human organs, ranging from breathing lungs to beating hearts. This technology is expected to be able to revolutionize cell biology studies, personalized precision medicine, drug development process, and cancer diagnosis/treatment. OOC systems can significantly reduce the cost associated with tedious drug development processes and the risk of adverse drug reactions in the body, which makes drug screening more effective. The review mainly focus on presenting an overview of the several previously developed OOC systems accompanied by subjects relevant to pharmacy‐, cancer‐, and placenta‐on‐a‐chip. The challenging issues and opportunities related to these systems are discussed, along with a future perspective for this technology.

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Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft‐Antenna

Sliow

Mahns

et al. 2019

Advanced Science

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An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft‐antenna). The graft‐antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft‐antenna and stimulated by the TMS for 1 h per week. The graft‐antenna is an innovative and minimally‐invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair.

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Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats

Cited by 119 publications

References 66 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

Human Organs‐on‐Chips: A Review of the State‐of‐the‐Art, Current Prospects, and Future Challenges

Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft‐Antenna

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