GADD34 gene restores virulence in viral vector used in experimental stroke study

doi:doi:10.1038/sj.jcbfm.9600565

Journal of Cerebral Blood Flow & Metabolism homepage

Journal of Cerebral Blood Flow & Metabolism (2008) 28, 747–751; doi:10.1038/sj.jcbfm.9600565; published online 10 October 2007

GADD34 gene restores virulence in viral vector used in experimental stroke study

Christopher McCabe¹, Fiona White^1,2, S Moira Brown² and I Mhairi Macrae¹

¹Division of Clinical Neuroscience, Wellcome Surgical Institute, Garscube Estate, University of Glasgow, Glasgow, UK
²Crusade Laboratories Ltd, Southern General Hospital, Glasgow, UK

Correspondence: Dr C McCabe, Division of Clinical Neuroscience, Wellcome Surgical Institute, Garscube Estate, University of Glasgow, Glasgow, Scotland G61 1QH, UK. E-mail: cmc39v@clinmed.gla.ac.uk

Received 18 July 2007; Revised 22 August 2007; Accepted 4 September 2007; Published online 10 October 2007.

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Abstract

GADD34 is expressed in the ischaemic brain and reverses protein synthesis shutdown. Consequently, GADD34 could have neuroprotective potential in stroke. BHK medium, a replication-deficient HSV viral vector (HSV1716) with no insert or containing full-length GADD34, the N terminal or a conserved portion of the gene, was injected into mouse brain before stroke. Infarct size was 1.0 plusminus 0.26, 1.190.36, 1.50.36, 1.30.36, and 1.10.28 mm³, respectively. The increase in infarct size with full-length GADD34 was statistically significant (P<0.05). Immunohistochemistry confirmed viral protein expression. Tissue culture studies revealed GADD34 gene restored virulence in HSV1716, suggesting that HSV virulence, rather than increased GADD34, exacerbated ischaemic damage.