Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation

Abstract

Neonatal sciatic nerve axotomy causes motoneuron death and muscle denervation atrophy. The aim of the present study was to determine whether insulin-like growth factor-I (IGF-I) administration promotes muscle reinnervation and counteracts motor neuron loss after such an injury. Six weeks after sciatic nerve axotomy performed in 2-day-old pups, the number of motor neurons, as assessed by retrograde transport of horseradish peroxidase injected into the extensor digitorum longus (EDL) muscle, was reduced from 52 +/- 3 to 26 +/- 3. Subsequent administration of IGF-I at the doses of 0.02 mg/kg or 1 mg/kg increased the number of motor neurons to 35 +/- 2 and 37 +/- 5, respectively. The effect on motoneuron survival was accompanied by improved muscle fibre morphometry and restoration of indirect EDL muscle isometric twitch tension, which was about 80 % of control values for both doses of IGF-I compared with 60% observed with saline treatment. Reinnervated EDL muscle from saline-treated rats cannot hold tetanic tension, which is, however, achieved after IGF-I treatment at either dose. Thus, both high and low doses of IGF-I counteracted motoneuron death and improved muscle reinnervation following neonatal sciatic nerve axotomy. IGF-I at 5 microg/kg failed to increase muscle reinnervation.

Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats

“…In the peripheral nervous system (PNS), IGF-1 is present in both the neurons and the skeletal muscles, and acts as a neurotrophic factor for motor, sensory, and sympathetic neurons to promote growth cone motility and neurite outgrowth. [11][12][13] It is also known that IGF-1 promotes neurite outgrowth in explants of adult rat retinas. 14 Such available evidence makes it clear that IGF-1 plays an important role in axonal regeneration and survival of CNS neurons as well as of those in the PNS.…”

Effect of locally delivered IGF‐1 on nerve regeneration during aging: An experimental study in rats

“…Vergani et al found that systemic IGF-1 promoted neuronal survival following crush injury and improved muscle reinnervation 34. Kanje et al found that locally delivered IGF-1 following crush injury in juveniles led to improved sensory function 35.…”

Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis

“…IGF-1 exerts a protective effect against motor neuron degeneration in organotypic spinal cord cultures [9,10] and cultured motor neurons [11], and is also capable of preventing motor neuron loss following sciatic nerve axotomy in rat pups [12]. Furthermore, it was reported to be effective against motor neuron loss in wobbler mice when co-administered with glycosaminoglycans that increase its permeability to the central nervous system (CNS) [13], whereas IGF-1 administration alone had no effect [14].…”