Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury

Int J Urol. 2013 Mar;20(3):344-8. doi: 10.1111/iju.12078. Epub 2013 Jan 17.

Abstract

Objectives: To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes.

Methods: Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition.

Results: Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P < 0.001). Maximum intracavernous pressure on electrostimulation was significantly elevated using glial cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons.

Conclusions: Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury.

MeSH terms

  • Analysis of Variance
  • Animals
  • Electric Stimulation
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / physiopathology
  • Erectile Dysfunction / therapy*
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Male
  • Nerve Regeneration*
  • Penile Erection / physiology*
  • Penis / innervation
  • Penis / physiopathology
  • Peripheral Nerve Injuries / complications
  • Peripheral Nerve Injuries / physiopathology
  • Peripheral Nerve Injuries / therapy*
  • Peripheral Nerves / physiology*
  • Pressure
  • Rats
  • Rats, Inbred F344
  • Recovery of Function*
  • Schwann Cells / metabolism*
  • Schwann Cells / transplantation
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Glial Cell Line-Derived Neurotrophic Factor