Systemic administration of rhIGF-I enhanced regeneration after sciatic nerve crush in mice.
Despite numerous reports suggesting that insulin-like growth factor-I (IGF-I) may be involved in the survival and regeneration of damaged neurons in vitro and after local administration in vivo, there have been few studies on the effect of IGF-I administered systemically on regeneration of damaged nerves in vivo and the functional consequences of enhanced regeneration. In an earlier study, recombinant human IGF-I (rhIGF-I) administered systemically enhanced the rate of regeneration after a sciatic crush as measured by the number of nerve fibers/muscle section. The purpose of this study was to follow up this finding by evaluating whether rhIGF-I administered peripherally enhances the rate of functional recovery. In this study following nerve injury, mice lost the ability to grip a wire screen with their hind paws and to walk normally as indicated by a decrease in toe spread, internal toe spread and an increase in the angle between hind feet. The ability of injured mice treated with rhIGF-I to grip an inverted screen returned to control levels significantly faster than that of vehicle-treated mice (day 12 vs. day 15, respectively). Similarly, rhIGF-I treatment of injured mice resulted in toe spread, internal toe spread and angle values that were significantly better than that of vehicle-treated mice and returned to control levels faster than vehicle-treated injured mice. There was a parallel loss of innervation after sciatic nerve crush as measured by a loss in choline acetyltransferase activity in the soleus and gastrocnemius muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Contreras
P C
PC
Cephalon Inc., West Chester, Pennsylvania, USA.
Steffler
C
C
Yu
E
E
Callison
K
K
Stong
D
D
Vaught
J L
JL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009416:Nerve Regeneration; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology*
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I