title: FK506-loaded chitosan conduit promotes the regeneration of injured sciatic nerves in the rat through the upregulation of brain-derived neurotrophic factor and TrkB.
abstract: FK506 has been shown to exert neurotrophic and neuroprotective effects, but its long-term application for nerve regeneration is limited. This study evaluated the potential application of a novel FK506-loaded chitosan conduit for peripheral nerve repair, and explored the underlying mechanism. A sciatic nerve injury model was created in male Wistar rats, which were then randomly divided into three treatment groups (n=40, each): chitosan-only, chitosan+FK506 injection, and FK506-loaded chitosan. We found significant recovery of normal morphology of sciatic nerves and higher density of myelinated nerve fibers in rats treated with FK506-loaded chitosan. Similarly, the total number of myelinated nerve fibers, myelin sheath thickness, and axon diameters were significantly higher in this group compared with the others, and the compound muscle action potentials and motor nerve conduction velocity values of sciatic nerves were significantly higher. BDNF and TrkB levels in motor neurons were highest in rats treated with FK506-loaded chitosan. In conclusion, FK506-loaded chitosan promoted peripheral nerve repair and regeneration in a rat model of sciatic nerve injury. These effects are correlated with increased BDNF and TrkB expression in motor neurons.
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China; DaLian the Sixth People's Hospital, Dalian 116031, China.
authors: Jia
authors: J
authors: Zhao
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
authors: Xifu
authors: X
authors: Zheng
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China. Electronic address: fuchongyang@hotmail.com.
authors: Chongyang
authors: C
authors: Fu
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China. Electronic address: quwei333@aliyun.com.
authors: Wei
authors: W
authors: Qu
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
authors: Guoqiang
authors: G
authors: Wei
authors: Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
authors: Weiguo
authors: W
authors: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D048271:Chitosan / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000188:drug therapy; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D019208:Brain-Derived Neurotrophic Factor; D004338:Drug Combinations; D019922:GAP-43 Protein; D007166:Immunosuppressive Agents; D048271:Chitosan; D020813:Receptor, trkB; D016559:Tacrolimus
keywords: BDNF; Chitosan; FK506; Nerve regeneration; Peripheral nerve injury; TrKB