Lentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal cord.
Cytotherapy
; 14(10): 1235-44, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23066785
ABSTRACT
BACKGROUND AIMS:
In this study we investigated the effect of neurotrophin-3 (NT-3) and knockdown of NG2, one of the main inhibitory chondroitin sulfate proteoglycans (CSPG), in the glial scar following spinal cord injury (SCI).METHODS:
Short hairpin (sh) RNA were designed to target NG2 and were cloned into a lentiviral vector (LV). A LV was also constructed containing NT-3. LV expressing NT-3, shRNA to NG2 or combinations of both vectors were injected directly into contused rat spinal cords 1 week post-injury. Six weeks post-injection of LV, spinal cords were examined by histology for changes in scar size and by immunohistochemistry for changes in expression of CSPG, NT-3, astrocytes, neurons and microglia/macrophages. Motor function was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor scale.RESULTS:
Animals that received the combination treatment of LV shNG2 and LV NT-3 showed reduced scar size. These animals also showed an increase in levels of neurons and NG2, a decrease in levels of astrocytes and a significant functional recovery as assessed using the BBB locomotor scale at 2 weeks post-treatment.CONCLUSIONS:
The improvement in locomotor recovery and decrease in scar size shows the potential of this gene therapy approach as a therapeutic treatment for SCI.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteoglicanas
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Traumatismos da Medula Espinal
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Terapia Genética
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Lentivirus
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Neurotrofina 3
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RNA Interferente Pequeno
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Locomoção
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Antígenos
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article