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dc.contributor.authorDonnelly, Eleanor M.
dc.contributor.authorMadigan, Nicolas N.
dc.contributor.authorRooney, Gemma E.
dc.contributor.authorKnight, Andrew
dc.contributor.authorChen, Bingkun
dc.contributor.authorBall, Bret
dc.contributor.authorKinnavane, Lisa
dc.contributor.authorGarcia, Yolanda
dc.contributor.authorDockery, Peter
dc.contributor.authorFraher, John
dc.contributor.authorStrappe, Padraig M.
dc.contributor.authorWindebank, Anthony J.
dc.contributor.authorO'Brien, Timothy
dc.contributor.authorMcMahon, Siobhan S.
dc.date.accessioned2019-08-26T13:12:46Z
dc.date.available2019-08-26T13:12:46Z
dc.date.issued2012-01-08
dc.identifier.citationDonnelly, Eleanor M., Madigan, Nicolas N., Rooney, Gemma E., Knight, Andrew, Chen, Bingkun, Ball, Bret, Kinnavane, Lisa, Garcia, Yolanda, Dockery, Peter, Fraher, John, Strappe, Padraig M., Windebank, Anthony J., O'Brien, Timothy, McMahon, Siobhan S. (2012). Lentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal cord. Cytotherapy, 14(10), 1235-1244. doi: https://doi.org/10.3109/14653249.2012.714865en_IE
dc.identifier.issn1477-2566
dc.identifier.urihttp://hdl.handle.net/10379/15347
dc.description.abstractBackground 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.en_IE
dc.description.sponsorshipWe wish to thank Professor Dider Trono (EFPL, Switzerland) for the kind gift of the lentiviral vector gene transfer and packaging plasmids. The authors wish to acknowledge the facilities and scientific assistance of the Centre for Microscopy and Imaging at the National University of Ireland Galway (www.imaging.nuigalway.ie), a facility that is funded by NUIG and the Irish Government's Programme for Research in third Level Institutions, Cycles 4 and 5, National Development Plan 2007–2013.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofCytotherapyen
dc.subjectastrocytesen_IE
dc.subjectaxon regenerationen_IE
dc.subjectchondroitin sulfate proteoglycansen_IE
dc.subjectglial scaren_IE
dc.subjectmicrogliaen_IE
dc.subjectneurotrophin-3en_IE
dc.subjectNG2en_IE
dc.subjectspinal cord injuryen_IE
dc.subjectNERVOUS-SYSTEM INJURYen_IE
dc.subjectAXONAL REGENERATIONen_IE
dc.subjectFUNCTIONAL RECOVERYen_IE
dc.subjectCHONDROITINASE ABCen_IE
dc.subjectNEURITE OUTGROWTHen_IE
dc.subjectGLIAL SCARen_IE
dc.subjectACTIVATED MACROPHAGESen_IE
dc.subjectINHIBITORY MOLECULESen_IE
dc.subjectREACTIVE ASTROCYTESen_IE
dc.subjectSENSORY NEURONSen_IE
dc.titleLentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal corden_IE
dc.typeArticleen_IE
dc.date.updated2014-02-24T22:17:11Z
dc.identifier.doi10.3109/14653249.2012.714865
dc.local.publishedsourcehttps://doi.org/10.3109/14653249.2012.714865en_IE
dc.description.peer-reviewedpeer-reviewed
dc.internal.rssid2929384
dc.local.contactSiobhan Mcmahon, Department Of Anatomy, Nui, Galway. 2838 Email: siobhan.mcmahon@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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