50 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)35-46
頁數12
期刊Journal of Neurosurgery: Spine
6
發行號1
DOIs
出版狀態已發佈 - 一月 2007

指紋

Insulin-Like Growth Factor I
Spinal Cord Injuries
Genes
Glycogen Synthase Kinase 3
Caspase 9
Phosphorylation
Neuroprotection
Apoptosis
Neurons
Neuronal Plasticity
Lac Operon
Nerve Growth Factors
Microglia
Hydrodynamics
Astrocytes
Intravenous Administration
Transfection
Sprague Dawley Rats
Tail
Veins

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

引用此文

@article{208b8a4614fe412e97d2c608468de7ee,
title = "Gene transfer of insulin-like growth factor-I providing neuroprotection after spinal cord injury in rats",
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.",
keywords = "Apoptosis, Gene transfer, Insulin-like growth factor-I, Spinal cord injury",
author = "Hung, {Kuo Sheng} and Tsai, {Shin Han} and Lee, {Tao Chen} and Lin, {Jia Wei} and Chang, {Cheng Kuei} and Chiu, {Wen Ta}",
year = "2007",
month = "1",
doi = "10.3171/spi.2007.6.1.35",
language = "English",
volume = "6",
pages = "35--46",
journal = "Journal of Neurosurgery: Spine",
issn = "1547-5654",
publisher = "American Association of Neurological Surgeons",
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TY - JOUR

T1 - Gene transfer of insulin-like growth factor-I providing neuroprotection after spinal cord injury in rats

AU - Hung, Kuo Sheng

AU - Tsai, Shin Han

AU - Lee, Tao Chen

AU - Lin, Jia Wei

AU - Chang, Cheng Kuei

AU - Chiu, Wen Ta

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Gene transfer

KW - Insulin-like growth factor-I

KW - Spinal cord injury

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