Neurotrophin-4 delivered by fibrin glue promotes peripheral nerve regeneration

Neurotrophin-4 (NT-4) is a recently identified neurotrophic factor with potential trophic effects on subpopulations of neurons. Little is known about its role in peripheral nerve regeneration following nerve injury. To investigate this, 48 Sprague-Dawley rats underwent left sciatic nerve transection and immediate repair. Fibrin glue mixed with either NT-4 or vehicle (control) was injected around the nerve repair site. Nerve regeneration was assessed both functionally and histomorphometrically. The results showed that the NT-4-treated group had a significant increase compared with the control in the regeneration distance at 5 days. The sciatic function index was significantly greater in the NT-4 group from 40 to 60 days after nerve repair. Morphometric analysis revealed that nerves treated with NT-4 had significant improvement in the number of regenerated axons, axonal diameter, and myelin thickness. These results suggest that NT-4 is a potent factor improving rat sciatic nerve regeneration.