Epothilone B loaded in acellular nerve allograft enhanced sciatic nerve regeneration in rats

• Published in: Fundamental & clinical pharmacology Vol. 38; no. 2; pp. 307 - 319
• Main Authors: Omar Khudhur, Zhikal, Ziyad Abdulqadir, Shang, Faqiyazdin Ahmed Mzury, Abdullah, Aziz Rasoul, Abdulrahman, Wasman Smail, Shukur, Ghayour, Mohammad B., Abdolmaleki, Arash
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-04-2024
• Subjects: allograft; Allografts; Atrophy; Axon sprouting; decellularization; Electrophysiology; EpoB; Epothilones; Histomorphometry; Latency; Nerves; Neuroprotection; Nucleotide sequence; Properties; Recovery; Regeneration; Regeneration (biological); Reinnervation; Sciatic nerve; Sensorimotor system; Stabilizers (agents); Stabilizing; decellularization; regeneration; allograft; EpoB; sciatic nerve
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12961

Background
Epothilone B (EpoB) is a microtubule‐stabilizing agent with neuroprotective properties.
Objectives
This study examines the regenerative properties of ANA supplemented with EpoB on a sciatic nerve deficit in male Wistar rats.
Methods
For this purpose, the 10 mm nerve gap was filled with acellular nerve allografts (ANAs) containing EpoB at 0.1, 1, and 10 nM concentrations. The sensorimotor recovery was evaluated up to 16 weeks after the operation. Real‐time PCR, histomorphometry analysis, and electrophysiological evaluation were also used to evaluate the process of nerve regeneration.
Results
ANA/EpoB (0.1 nM) significantly improved sensorimotor recovery in rats compared to ANA, ANA/EpoB (1 nM), and ANA/EpoB (10 nM) groups. This led to reduced muscle atrophy, improved sciatic functional index, and thermal paw withdrawal reflex latency, indicating nerve regeneration and target organ reinnervation. The electrophysiological and histomorphometry findings also confirmed the ANA/EpoB regenerative properties (0.1 nM). EpoB only enhanced ANA regenerative properties at 0.1 nM, with no therapeutic effects at higher concentrations.
Conclusion
Totally, we concluded that ANA loaded with 0.1 nM EpoB can effectively reconstruct the transected sciatic nerve in rats, likely by enhancing axonal sprouting and extension.