LOCAL-ADMINISTRATION OF THYROID-HORMONES IN SILICONE CHAMBER INCREASES REGENERATION OF RAT TRANSECTED SCIATIC-NERVE

Conflicting actions of the exogenous thyroid hormone on regenerating p eripheral nerve have been reported. These contradictory results were p robably due to daily intraperitoneal injections which induce a high co ncentration of thyroid hormone after administration. In our present st udy we adapted a technique which allows a local administration of thyr oid hormones in a closed system. The effect of a single and local trea tment with triiodothyronine (T-3) on axonal growth across a gap betwee n sectioned ends of sciatic nerve within silicone chambers was examine d in Wistar rats. After nerve transection and surgical implantation, s ilicone chambers were filled with either a neutral pH solution of trii odothyronine dissolved in NaOH or with sterile solvent as control. Reg eneration of the nerves was examined 2 to 8 weeks following the surger y. Early regeneration (4 weeks) was studied by morphological analysis of nerves which showed a significant difference between T-3-treated an d control groups. Morphometric analysis revealed: (1) a significant di fference in the mean diameter of myelinated axons between T-3-treated nerve (empty set 3.80 +/- 0.22 mu m) and control (o 3.07 +/- 0.44 pm); (2) that T-3 increased significantly (1.4-fold) the number of myelina ted axons that grew into the middle and distal ends of regeneration ch ambers; (3) that ultrastructural analysis showed significantly higher percentage of myelinated axons per total axon population in T-3-treate d groups (38.8 +/- 5.9%) as compared to control (16.0 +/- 2.3%); and ( 4) that the myelinated axons had thicker myelin sheaths. The beneficia l effects of T-3 On regeneration, observed at 4 weeks, were sustained over a prolonged period of time. Thus, at 8 weeks of regeneration, the number, the mean diameter of myelinated axons, and the thickness of m yelin sheaths remained significantly greater in T-3-treated groups. Th erefore, a single and local administration of thyroid hormone at the l evel of the transected sciatic nerve is sufficient to rapidly set off several mechanisms which, in turn, produce a stimulating and lasting e ffect on peripheral nerve regeneration. The beneficial effects of T-3 upon injured peripheral nerve may have considerable therapeutic potent ial. (C) 1998 Academic Press.