Polyethylene Glycol Rapidly Restores Axonal Integrity and Improves the Rate of Motor Behavior Recovery After Sciatic Nerve Crush Injury

Abstract

The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24–48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4–8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.