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.
Original language | English |
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Pages (from-to) | 1235-44 |
Number of pages | 10 |
Journal | Cytotherapy |
Volume | 14 |
Issue number | 10 |
DOIs | |
Publication status | Published - Nov 2012 |
Keywords
- Animals
- Antigens/genetics
- CD11b Antigen/metabolism
- Cellular Microenvironment
- Chondroitin Sulfate Proteoglycans/metabolism
- Cicatrix/pathology
- Female
- Gene Transfer Techniques
- Genetic Therapy
- Genetic Vectors/genetics
- Glial Fibrillary Acidic Protein/metabolism
- Immunohistochemistry
- Lentivirus/genetics
- Locomotion
- Neurotrophin 3/genetics
- Proteoglycans/genetics
- RNA, Small Interfering/administration & dosage
- Rats
- Rats, Sprague-Dawley
- Recovery of Function
- Spinal Cord Injuries/pathology
- Staining and Labeling
- Tubulin/metabolism