Repair with collagen tubules linked with brain-derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model.
OBJECTIVE
To determine if brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) can be successfully delivered to transected and repaired peripheral nerves by cross-linking the factors to collagen tubules (CTs).


METHODS
Forty-eight Sprague-Dawley rats underwent left sciatic nerve transection and repair. In the control group, CTs were implanted with no neurotrophic ligand (n=13). There were 3 experimental groups: CT with BDNF covalently linked to the collagen matrix (CT/BDNF; n=12), CT with CNTF covalently linked (CT/CNTF; n=12), and CT with both BDNF and CNTF covalently linked (CT/BDNF/CNTF; n=11). Functional outcome of neural regeneration was assessed every 10 days using walking track analysis, which was submitted to a sciatic functional index. Nerve morphometry, electrophysiologic studies, and molecular analysis for neural proteins were performed at the completion of the study at postoperative day 90.


RESULTS
Animals in all 3 experimental groups achieved significantly superior maximal functional recovery, larger nerve cross-sectional areas, and a greater number of axons when compared with the control CT group (P<.001, P<.05, and P<.05, respectively). The animals in the CT/BDNF/CNTF group displayed the best functional recovery and had the largest axon diameters, greatest amplitude, and the fastest nerve conduction velocities. Molecular analysis revealed significant differences in the expression of neurofilament, neural cell adhesion molecule, myelin-associated glycoprotein, and myelin basic protein.


CONCLUSIONS
We present the first evidence that CNTF covalently linked to CTs can improve functional recovery compared with CTs alone. We also support the previous finding that BDNF covalently linked to CTs significantly increases the functional recovery of transected and repaired nerves. Finally, we found that cotreatment produced the best functional recovery in our model.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Calif 94305-5328, USA.
P R
PR
Ho
G M
GM
Coan
E T
ET
Cheng
C
C
Niell
D M
DM
Tarn
H
H
Zhou
D
D
Sierra
D J
DJ
Terris
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D020934:Ciliary Neurotrophic Factor; D003094:Collagen / Q000627:therapeutic use*; D004558:Electric Stimulation; D004594:Electrophysiology; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D019006:Neural Cell Adhesion Molecules; D009431:Neural Conduction; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology / Q000601:surgery*
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D003094:Collagen