The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model

Abstract

Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: “ES” and “Control.” Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair.

Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats

“…However, previous animal work using electrical stimulation has demonstrated efficacy in these acute nerve injury models. 11,33,34 Therefore, it seems promising that this protocol could be efficacious in these clinically relevant situations, given the translation of 60-minute electrical stimulation protocols from similar preclinical models.…”

“…However, previous animal work using electrical stimulation has demonstrated efficacy in these acute nerve injury models. 11,33,34 Therefore, it seems promising that this protocol…”

“…Most studies involving either animals or clinical trials have used a 1-hour electrical stimulation protocol. 10,11,15 However, the use of electrical stimulation for less than 1 hour (and even as short as 10 minutes) to achieve a therapeutic effect during nerve regeneration has precedence 22,[28][29][30][31] ; however, these shorter protocols have never been directly compared to the prominent 1-hour electrical stimulation protocol championed by others and as performed in our studies.…”

The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury

“…ES has also been investigated to improve nerve regeneration following other types of nerve injury. Keane et al showed in a murine model that one-hour of ES (16 Hz, 100 μsec) delivered after isograft reconstruction (1 cm) accelerated functional recovery compared to controls [ 25 ]. This study demonstrated the clinical potential of ES therapy to improve patient outcomes following more severe nerve injuries requiring nerve graft reconstruction [ 25 ].…”

“…ES has been shown to promote the expression of regeneration associated genes (RAG) and cytoskeletal proteins which promote neuronal survival and axonal outgrowth [ 21 , 22 ]. The application of ES in rodent injury models has demonstrated improved functional outcomes following the repair of crush [ 23 ], transection [ 18 , 20 ], and large gap injuries [ 24 , 25 ]. Recently published human clinical trials have also demonstrated encouraging results for perioperative ES in a subset of PNIs.…”