The effect of antibodies to TGF-beta1 and TGF-beta2 at a site of sciatic nerve repair.
Scar formation at a site of nerve injury can cause a mechanical barrier to axonal regeneration and lead to the development of multiple axonal sprouts to form a neuroma. We have investigated the hypothesis that the application of a scar-preventing agent to a nerve repair site would enhance regeneration of the nerve and reduce neuroma formation. The left sciatic nerve was exposed under general anaesthesia in 18 adult Sprague-Dawley rats. In 12 animals, the nerve was sectioned and immediately re-approximated using four epineurial sutures, and in 6 of these animals neutralising antibodies to transforming growth factor (TGF)-beta1 and TGF-beta2 were injected into and around the repair site. The six other animals acted as controls. After 7 weeks, the outcome was assessed by recording compound action potential (CAP) ratios, measuring collagen levels using picrosirius red staining, and counting the number of myelinated axons proximal and distal to the repair. After repair alone, the mean percentage of area of staining (PAS) for collagen within the nerve had significantly increased. However, after repair with the administration of antibodies, the PAS was not significantly different from that in the sham controls. After administration of antibodies, the CAP ratios were significantly smaller than in controls but not after repair alone. In both nerve injury groups, the myelinated fibre counts were significantly increased distal to the injury site, but there was no difference between these two groups. We conclude that administration of antibodies to TGF-beta1 and TGF-beta2 reduced scar formation at the repair site but did not enhance regeneration of the nerve or reduce the development of multiple axonal sprouts.
Atkins
Simon
S
Department of Oral and Maxillofacial Surgery, University of Sheffield; and Faculty of Life Sciences, University of Manchester, Manchester, UK.
Smith
Keith G
KG
Loescher
Alison R
AR
Boissonade
Fiona M
FM
Ferguson
Mark W J
MW
Robinson
Peter P
PP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D019771:Axotomy; D002921:Cicatrix / Q000517:prevention & control*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009463:Neuroma / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000293:injuries*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors* / Q000276:immunology
D000906:Antibodies; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2