F. Voinesco et al., LOCAL-ADMINISTRATION OF THYROID-HORMONES IN SILICONE CHAMBER INCREASES REGENERATION OF RAT TRANSECTED SCIATIC-NERVE, Experimental neurology, 150(1), 1998, pp. 69-81
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.