Effects of Repeated 20-Hz Electrical Stimulation on Functional Recovery Following Peripheral Nerve Injury

• Type of Material: Article
• Authors: Sohee Park, Emory University; Cai-Yue Liu, Shanghai Jiao Tong University; Patricia Ward, Emory University; Poonam B. Jaiswal, Emory University; Arthur English, Emory University
• Language: English
• Date: 2019-07-22
• Publisher: Sage Publications Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author(s) 2019.
• Final Published Version (URL): http://dx.doi.org/10.1177/1545968319862563
• Title of Journal or Parent Work: Neurorehabilitation and Neural Repair
• Volume: 33
• Issue: 9
• Start Page: 775
• End Page: 784
• Grant/Funding Information: Supported by grants NS057190 and HD032571 from the USPHS.
• Keywords: Life Sciences & Biomedicine; electrical stimulation; Regenerating motoneurons; Strategies; VGLUT1 synapses; Expression; Science & Technology; Neurosciences & Neurology; Clinical Neurology; Proprioceptors; Rehabilitation; regeneration; BDNF; Exercise; Axon regeneration; Gabaergic terminals; Facilitation; Central synaptic disconnection; peripheral nerves
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience; Biology, Cell

Abstract

One hour of 20-Hz continuous electrical stimulation (ES) applied at the time of injury promotes the regeneration of axons in cut peripheral nerves. A more robust enhancement of peripheral axon regeneration is achieved by 2 weeks of daily treadmill exercise. We investigated whether repeated applications of brief ES (mES) would be more effective in promoting regeneration than a single application. Sciatic nerves of C57B6 mice were cut and repaired by end-to-end anastomosis. At that time and every third day for 2 weeks, the repaired nerve was stimulated for 1 hour at 20 Hz. In controls, injured mice were either untreated or treated with ES only once. Direct muscle responses recorded from reinnervated muscles in awake animals were observed earlier both in mice treated with ES and mES than untreated controls. Their amplitudes increased progressively over the post transection study period, but the rate of this progression was increased significantly only in animals treated once with ES. Monosynaptic H reflexes recovered to pretransection levels in both untreated and singly treated mice but in the animals treated repeatedly, they were maintained at more than twice that of the same reflexes recorded prior to injury. In anatomical analyses, both excitatory and inhibitory synaptic contacts with the cell bodies of injured motoneurons, including those expressing the vesicular glutamate transporter 1 (VGLUT1), were sustained in mice treated repeatedly but not in singly treated or untreated mice. Repeated ES does not enhance the rate of restoration of functional muscle reinnervation and results in the retention of exaggerated reflexes.