Behavioral recovery and spinal motoneuron remodeling after polyethylene glycol fusion repair of singly cut and ablated sciatic nerves.

Cameron L Ghergherehchi,Emily A Hibbard,Dale R Sengelaub,Michelle Mikesh,George D Bittner,William D Phillips

doi:10.1371/journal.pone.0223443

Cameron L Ghergherehchi, Emily A Hibbard + Show 4 more

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https://doi.org/10.1371/journal.pone.0223443

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Abstract

Polyethylene glycol repair (PEG-fusion) of severed sciatic axons restores their axoplasmic and membrane continuity, prevents Wallerian degeneration, maintains muscle fiber innervation, and greatly improves recovery of voluntary behaviors. We examined alterations in spinal connectivity and motoneuron dendritic morphology as one potential mechanism for improved behavioral function after PEG-fusion. At 2–112 days after a single-cut or allograft PEG-fusion repair of transected or ablated sciatic nerves, the number, size, location, and morphology of motoneurons projecting to the tibialis anterior muscle were assessed by retrograde labeling. For both lesion types, labeled motoneurons were found in the appropriate original spinal segment, but also in inappropriate segments, indicating mis-pairings of proximal-distal segments of PEG-fused motor axons. Although the number and somal size of motoneurons was unaffected, dendritic distributions were altered, indicating that PEG-fusion preserves spinal motoneurons but reorganizes their connectivity. This spinal reorganization may contribute to the remarkable behavioral recovery seen after PEG-fusion repair.

Highlights

Peripheral nerve injuries (PNIs) that disrupt axonal continuity have many effects on peripheral nervous system (PNS) structure and function, such as the immediate loss of voluntary motor control, sensory reception, rapid degeneration of the distal axonal segments (Wallerian degeneration), loss of neuromuscular junction (NMJ) innervation, and muscle fiber atrophy [1]
Our stimulation of intact sciatic nerves (n = 98) always produced compound action potential (CAP) recorded from the nerve or compound muscle action potential (CMAP) recorded from the tibialis anterior (TA) muscle (Fig 2A and 2B) or other sciatic-innervated muscles
These CMAPs are no longer observed if the collateral branch is subsequently transected.) CAPS and CMAPs were not restored after microsuture repair in Negative Control Single Cut nerves (n = 13), i.e., if the polyethylene glycol (PEG)-solution was not applied, axonal continuity was not restored by neurorrhaphy alone (Fig 2A and 2B)

Summary

Introduction

Peripheral nerve injuries (PNIs) that disrupt axonal continuity (axotomy) have many effects on peripheral nervous system (PNS) structure and function, such as the immediate loss of voluntary motor control, sensory reception, rapid degeneration of the distal axonal segments (Wallerian degeneration), loss of neuromuscular junction (NMJ) innervation, and muscle fiber atrophy [1]. In addition to these PNS changes after PNIs, changes occur in the central nervous system (CNS) as well. These PNI-induced changes include somal atrophy [4, 8] and withdrawal of synaptic inputs

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