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Donnelly, EM,Madigan, NN,Rooney, GE,Knight, A,Chen, BK,Ball, B,Kinnavane, L,Garcia, Y,Dockery, P,Fraher, J,Strappe, PM,Windebank, AJ,O'Brien, T,McMahon, SS
2012
January
Cytotherapy
Lentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal cord
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Optional Fields
astrocytes axon regeneration chondroitin sulfate proteoglycans glial scar microglia neurotrophin-3 NG2 spinal cord injury AXONAL REGENERATION FUNCTIONAL RECOVERY CHONDROITINASE ABC NEURITE OUTGROWTH NERVOUS-SYSTEM ACTIVATED MACROPHAGES DORSAL COLUMNS SENSORY AXONS CNS INJURY PROTEOGLYCAN
14
1235
1244
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.
DOI 10.3109/14653249.2012.714865
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