Neuroregenerative effects of polyethylene glycol and FK-506 in a rat model of sciatic nerve injury

Adriana M Paskal; Wiktor Paskal; Piotr Pietruski; Zofia Kusmierczyk; Ewa Jankowska-Steifer; Jaroslaw Andrychowski; Pawel K Wlodarski

doi:10.1016/j.bjps.2019.10.011

Neuroregenerative effects of polyethylene glycol and FK-506 in a rat model of sciatic nerve injury

J Plast Reconstr Aesthet Surg. 2020 Feb;73(2):222-230. doi: 10.1016/j.bjps.2019.10.011. Epub 2019 Oct 11.

Authors

Adriana M Paskal¹, Wiktor Paskal², Piotr Pietruski³, Zofia Kusmierczyk⁴, Ewa Jankowska-Steifer⁵, Jaroslaw Andrychowski⁶, Pawel K Wlodarski⁷

Affiliations

¹ Department of Methodology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
² Department of Methodology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: wiktor.paskal@wum.edu.pl.
³ Timeless Plastic Surgery Clinic, gen. Romana Abrahama 18/322, 03-982 Warsaw, Poland.
⁴ Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
⁵ Department of Histology and Embryology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: ewa.jankowska-steifer@wum.edu.pl.
⁶ Department of Neurology and Neurosurgery, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland. Electronic address: j.andrychowski@wp.pl.
⁷ Department of Methodology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: pawel.wlodarski@wum.edu.pl.

PMID: 31759923
DOI: 10.1016/j.bjps.2019.10.011

Abstract

The recently introduced polyethylene glycol (PEG) treatment restores axonal continuity after nerve injury, leading to rapid recovery of nerve function. The impact of PEG therapy on neuroregeneration has not yet been compared with any intervention with an established proneuroregenerative potential. FK-506 is an immunosuppressive agent with documented proneuroregenerative potential in nerve injury models. The aim of this study was to compare the effects of PEG therapy and preinjury FK-506 administration in rats with sciatic nerve transection injury. Four groups of male Sprague Dawley rats (seven per group) underwent sciatic nerve transection with primary repair. Group A received placebo injections, group B placebo injections and PEG treatment, group C FK-506 injections, and group D both FK-506 injections and PEG treatment. Clinical outcomes were assessed by the skin prick test and Sciatic Functional Index (SFI). Regenerated nerves underwent histomorphometric analysis. The histomorphometric analysis demonstrated that compared with the controls, nerve specimens from all treated groups showed signs of enhanced neuroregeneration (higher mean axonal area) (p < 0.001). The histomorphometric parameters for group D (PEG + FK-506), mean axonal area (p < 0.001) and axonal count (p > 0.05), were significantly better than those in the other study groups. The Form factor was closest to its optimal values in group B (p < 0.0001). At the end of the study, mean skin prick test scores in all treated groups were significantly higher than those in controls (p > 0.05). During the first postoperative week, PEG-treated rats (groups B and D) presented with higher values of the SFI than animals from groups A and C, but the difference was not statistically significant. Combined therapy with PEG and FK-506 seems to produce better neuroregeneration outcomes than a simple suture-based repair complemented with either PEG or FK-506 treatment.

Keywords: FK-506; Nerve injury; Neuroregeneration; Polyethylene glycol; Rat.

MeSH terms

Animals
Disease Models, Animal
Male
Nerve Regeneration / drug effects*
Peripheral Nerve Injuries / drug therapy*
Polyethylene Glycols / pharmacology*
Rats
Rats, Sprague-Dawley
Sciatic Nerve / drug effects*
Sciatic Nerve / injuries
Sciatic Nerve / physiology*
Sciatic Neuropathy / drug therapy*
Tacrolimus / pharmacology*

Substances

Polyethylene Glycols
Tacrolimus