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Article type: Research Article
Authors: Groutsi, F. | Mason, M.R.J.; | Anderson, P.N. | Martins, S. | Anesti, M. | Coffin, R.S. | Campbell, G.
Affiliations: Biovex Ltd, Windeyer Building, Cleveland Street, London, UK | Department of Anatomy and Developmental Biology, University College London, Gower Street, London, UK
Note: [] Corresponding author: Dr G. Campbell, Department of Cell & Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. Tel.: +44 020 7679 7764; Fax: +44 020 7679 7349; E-mail: g.campbell@ucl.ac.uk
Abstract: Purpose: The primary motor pathway, the corticospinal tract, is a major target for spinal cord regeneration studies. One way of improving the regeneration of corticospinal axons is to introduce regeneration-associated genes into cortical motor neurons using viral vector delivery. Methods: We used an engineered Herpes Simplex virus (HSV1) with the EF1α promoter encoding either LacZ or GFP to transduce cortical neurons through retrograde transport following the injection of vector into adult rat striatum or spinal cord. After three-days to one-month post-injection, sections of brain and spinal cord were viewed with fluorescence microscopy or processed for LacZ histochemistry. Results: Many layer V motor cortical neurons were transduced following striatal injections. These were not corticospinal neurons as they were not fluorogold-labelled following tracer injection into spinal cord. Corticospinal neurons in both hemispheres were, however, transduced following direct vector injections into the dorsal column of spinal cord, yielding 250–400 transduced corticospinal neurons per animal. No non-pyramidal neurons or thalamic neurons were transduced by spinal injections. Conclusions: Therefore, this HSV1.EF1α vector is highly effective for the transduction of corticospinal neurons without direct injection into the brain and could be used to introduce regeneration-relevant genes into these neurons with the aim of regenerating the corticospinal tract.
Keywords: In vivo transduction, corticospinal neurons, HSV1 vector, elongation factor 1α, rat
Journal: Restorative Neurology and Neuroscience, vol. 26, no. 6, pp. 509-520, 2008
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