title: IGF-I and end-to-side nerve repair: a dose-response study.
abstract: End-to-side nerve repair allows for target-muscle reinnervation, with simultaneous preservation of donor-nerve function. Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerve. The purpose of the current project was to determine the effects of IGF-I in a rat model of end-to-side nerve repair. The left musculocutaneous nerve of 18 adult male Sprague-Dawley rats was fully transected to induce biceps-muscle paralysis. The distal stump of the musculocutaneous nerve was then coapted by end-to-side neurorrhaphy through a perineurial window to the ipsilateral median nerve. All animals were randomly assigned to three groups: Group A received 100 microg/ml IGF-I; Group B received 50 microg/ml IGF-I; and control Group C received 10 mM acetic acid vehicle solution. Infusions were regulated by the Alzet model 2004 mini-osmotic pump, with an attached catheter directed at the coaptation site. Weekly postoperative behavioral evaluations revealed significantly increased functional return over control in both experimental groups as early as 3 weeks. After 28 days, histology evaluations revealed statistically significantly higher musculocutaneous nerve axon counts and myelin thickness/axon diameter ratios in both experimental groups vs. controls. The three groups were not significantly different in motor endplate counts of the biceps muscle. Groups A and B were not significantly different in all parameters tested. This study suggests that local infusion of IGF-I may expedite the functional recovery of a paralyzed muscle, by increasing the rate of axon regeneration through an end-to-side nerve graft.
authors.affiliation: Eastern Virginia Medical School, Microsurgical Research Center, Norfolk 23501, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Tiangco
authors.forename: K C
authors.initials: KC
authors.lastname: Papakonstantinou
authors.forename: K A
authors.initials: KA
authors.lastname: Mullinax
authors.forename: J K
authors.initials: JK
authors.lastname: Terzis
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology; D009416:Nerve Regeneration / Q000187:drug effects*; D016067:Nerve Transfer; D010525:Peripheral Nerves / Q000166:cytology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007334:Insulin-Like Growth Factor I