Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone.
The objective was to investigate the effects of brain-derived neurotropic factor (BDNF) and ciliary neurotropic factor (CNTF) on peripheral nerve regeneration. Thirty Sprague-Dawley rats underwent left sciatic nerve transection and repair according to three experimental groups: epineurial coaptation (EC), EC with BDNF delivered by an osmotic pump (EC-BDNF), and EC with BDNF and CNTF delivered similarly (EC-BDNF/CNTF). Nerve regeneration was assessed using sciatic functional indices, quantitative histomorphology, and molecular analysis for proteins associated with nerve regeneration. Analysis of variance (ANOVA) comparing all groups at each time point demonstrated significant differences between groups on days 20, 30, 40, 50, 60, and 80. A paired, two-tailed Student's t-test with the Bonferroni correction for multiple comparisons demonstrated that at 40 days postoperatively, animals in the EC-BDNF/CNTF group (n = 7) manifested superior functional recovery compared with those in the EC group (n = 9) and those in the EC-BDNF group (n = 9) (P < 0.001 and P < 0.05, respectively). At 80 days, the animals in both the EC-BDNF (P < 0.01) and EC-BDNF/CNTF (P < 0.05) groups demonstrated greater functional recovery compared with those in the EC group, with no significant difference between the two factor groups at the endpoint. Morphometric analysis demonstrated that nerves from animals in the EC-BDNF/CNTF group had the largest mean axon diameters as compared with those from the EC (proximal: P < 0.001, distal: P < 0.05) and EC-BDNF (proximal: P < 0.01) groups. No significant differences were seen in nerve cross-sectional area. In distal nerve segments, Western blot analysis revealed that expression of myelin-associated glycoprotein was higher than control for the EC group and lower than control for both the EC-BDNF and EC-BDNF/CNTF groups. We conclude that BDNF/CNTF combined treatment increases the early rate of functional sciatic nerve regeneration over treatment with BDNF alone, although the degree of maximal recovery was similar at the conclusion of the experiment.
Lewin
S L
SL
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, California 94305-5328, USA.
Utley
D S
DS
Cheng
E T
ET
Verity
A N
AN
Terris
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D020934:Ciliary Neurotrophic Factor; D004338:Drug Combinations; D006614:Hindlimb; D007260:Infusion Pumps; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology; D004676:Myelin Basic Protein / Q000032:analysis; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016037:Single-Blind Method; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D004338:Drug Combinations; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins