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Lentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal cord

journal contribution
posted on 06.11.2018, 00:00 by EM Donnelly, NN Madigan, GE Rooney, A Knight, B Chen, B Ball, L Kinnavane, Y Garcia, P Dockery, J Fraher
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. © 2012 Informa Healthcare.

History

Volume

14

Issue

10

Start Page

1235

End Page

1244

Number of Pages

10

eISSN

1477-2566

ISSN

1465-3249

Publisher

Elsevier, UK

Peer Reviewed

Yes

Open Access

No

Acceptance Date

19/07/2012

External Author Affiliations

Mayo Clinic, USA; National University Ireland; University College Cork, Ireland

Era Eligible

Yes

Journal

Cytotherapy