A Novel Approach to Peripheral Nerve Regeneration: Local FK-506 Delivery Using a Reservoir Flap Model

Yonsei Med J. 2024 Dec;65(12):718-726. doi: 10.3349/ymj.2024.0351.

Abstract

Purpose: Peripheral nerve injuries can lead to lasting functional impairments, impacting movement and quality of life. FK-506, a widely used immunosuppressant, has demonstrated potential in promoting nerve regeneration in addition to its immunosuppressive effects. This study investigates the use of a local reservoir flap to deliver FK-506 directly to the nerve injury site, aiming to enhance nerve regeneration while minimizing systemic immunosuppression.

Materials and methods: Sciatic nerve injuries were surgically induced in 24 rats, which were divided into control, 0.5 mg/kg FK-506 (Exp 1), and 2.0 mg/kg FK-506 (Exp 2) groups. A superficial inferior epigastric artery flap served as a reservoir for FK-506, allowing direct delivery to the injury site. FK-506 was administered intermittently over a 4-week period. Outcomes included the Sciatic Functional Index (SFI), muscle recovery (width and weight), nerve morphology, expression of neurogenic markers such as GDNF, immune cell counts, and body weight.

Results: Exp 1 (0.5 mg/kg) demonstrated significant improvements in SFI, GDNF expression, and muscle width compared to the control and high-dose groups. These findings suggest that FK-506 administration via a reservoir flap, particularly at a lower dose, supports effective nerve regeneration. Additionally, FK-506 treatment did not result in significant changes in immune cell profiles or body weight, indicating minimal systemic effects.

Conclusion: Localized FK-506 administration via a reservoir flap effectively enhances peripheral nerve regeneration and minimizes systemic immunosuppression, making it a promising approach for clinical application in treating peripheral nerve injuries.

Keywords: Peripheral nerve injury; immunosuppression; nerve regeneration.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glial Cell Line-Derived Neurotrophic Factor
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Nerve Regeneration* / drug effects
  • Peripheral Nerve Injuries* / drug therapy
  • Peripheral Nerve Injuries* / surgery
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve* / drug effects
  • Sciatic Nerve* / injuries
  • Sciatic Nerve* / physiology
  • Surgical Flaps
  • Tacrolimus* / administration & dosage
  • Tacrolimus* / pharmacology
  • Tacrolimus* / therapeutic use

Substances

  • Tacrolimus
  • Immunosuppressive Agents
  • Glial Cell Line-Derived Neurotrophic Factor