Abstract
Facial nerve trauma often leads to disfiguring facial muscle paralysis. Despite several promising advancements, facial nerve repair procedures often do not lead to complete functional recovery. Development of novel repair strategies requires testing in relevant preclinical models that replicate key clinical features. Several studies have reported that fusogens, such as polyethylene glycol (PEG), can improve functional recovery by enabling immediate reconnection of injured axons; however, these findings have yet to be demonstrated in a large animal model. We first describe a porcine model of facial nerve injury and repair, including the relevant anatomy, surgical approach, and naive nerve morphometry. Next, we report positive findings from a proof-of-concept experiment testing whether a neurorrhaphy performed in conjunction with a PEG solution maintained electrophysiological nerve conduction at an acute time point in a large animal model. The buccal branch of the facial nerve was transected and then immediately repaired by direct anastomosis and PEG application. Immediate electrical conduction was recorded in the PEG-fused nerves (n = 9/9), whereas no signal was obtained in a control cohort lacking calcium chelating agent in one step (n = 0/3) and in the no PEG control group (n = 0/5). Nerve histology revealed putative-fused axons across the repair site, whereas no positive signal was observed in the controls. Rapid electrophysiological recovery following nerve fusion in a highly translatable porcine model of nerve injury supports previous studies suggesting neurorrhaphy supplemented with PEG may be a promising strategy for severe nerve injury. While acute PEG-mediated axon conduction is promising, additional work is necessary to determine if physical axon fusion occurs and the longer-term fate of distal axon segments as related to functional recovery.
Highlights
Facial nerve palsy resulting from facial nerve injury is a devastating, disfiguring condition, diagnosed in ∼20 in 100,000 patients annually [1]
Recent findings in rodent models have suggested that polyethylene glycol (PEG) fusion may mitigate the harmful effects of prolonged denervation by preventing Wallerian degeneration and rapidly restoring the electrophysiological connection of some axons
We found direct facial nerve anastomosis with PEG fusion protocols immediately enabled a measurable Compound nerve action potentials (CNAPs) across the suture site that resulted in an evoked snout twitch similar to previous studies
Summary
Facial nerve palsy resulting from facial nerve injury is a devastating, disfiguring condition, diagnosed in ∼20 in 100,000 patients annually [1]. Muscle paralysis may occur from trauma to the facial nerve and resultant denervation of the facial muscle [2]. After the nerve injury, transected axons rapidly seal to prevent further damage via calcium influx and calcium-mediated vesicular formation [5]. After 3–7 days, the disconnected distal axonal segments undergo fragmentation and eventually myelin clearance [6]. Fusogens, such as polyethylene glycol (PEG), are a promising approach for nerve repair that are posited to immediately restore axonal continuity, and thereby preventing Wallerian degeneration [7–10]. After administering calcium-free hypotonic saline to prevent calcium influx and an antioxidant to prevent freeradical formation as well as vesicular formation, fusogens can be applied which may rapidly restore the connection between the unsealed proximal axons in close opposition to unsealed distal axons. It has been suggested that the successful execution of the fusogen protocol facilitates the reconnection of otherwise transected axonal membranes, allowing for immediate electrophysiological connectivity
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