Abstract

Object. Insulin-like growth factor-I (IGF-I) has been shown to be a potent neurotrophic factor that promotes the growth of projection neurons, dendritic arborization, and synaptogenesis. Its neuroprotective roles may be coordinated by activation of Akt, inhibition of glycogen synthase kinase-3β (GSK-3β), and thus inhibition of tau phosphorylation. The authors investigated the role and mechanism of IGF-I gene transfer after spinal cord injury (SCI). Methods. Studies were performed in 40 male Sprague-Dawley rats after spinal cord hemisection. The authors conducted hydrodynamics-based gene transfection in which an IGF-I plasmid was rapidly injected into the rat's tail vein 30 minutes after SCI. The animals were randomly divided into four groups: Group I, sham operated; Group II, SCI treated with pCMV-IGF-I gene; Group III, SCI treated with vehicle pCMV-LacZ gene; and Group IV, SCI only. The results showed that IGF-I gene transfer promoted motor recovery, antiinflammatory responses, and antiapoptotic effects after SCI. Using techniques of Western blotting and immunohistochemistry, the authors assessed the mechanism of IGF-I gene transfer after SCI in terms of activation of Akt, inhibition of GSK-3β, attenuation of p35, and inhibition of tau phosphorylation. Moreover, they found that IGF-I gene transfer could block caspase-9 cleavage, increase Bcl-2 formation, and thus inhibit apoptosis after SCI. Conclusions. The intravenous administration of IGF-I after SCI activated Akt, attenuated GSK-3β, inhibited p35 activation, diminished tau hyperphosphorylation, ended microglia and astrocyte activation, inhibited neuron loss, and significantly improved neurological dysfunction. Furthermore, IGF-I attenuated caspase-9 cleavage, increased Bcl2, and thus inhibited apoptosis after SCI.

Original languageEnglish
Pages (from-to)35-46
Number of pages12
JournalJournal of Neurosurgery: Spine
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Apoptosis
  • Gene transfer
  • Insulin-like growth factor-I
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

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