1. ¹RCS Unit of Biophysics, Institute of Child Health, University College London, London, UK
2. ²Wellcome Trust High Field MR Research Laboratory, Department of Medical Physics, University College London, London, UK
3. ³Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK

Correspondence: R Aron Badin, RCS Unit of Biophysics, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. E-mail: R.Aron-Badin@ich.ucl.ac.uk

Received 18 February 2005; Revised 16 June 2005; Accepted 17 June 2005; Published online 3 August 2005.

Abstract

Heat shock proteins (HSPs) are molecular chaperones with essential roles in modulating the proteolytic machinery and accelerating cell repair. Heat shock protein overexpression has been observed in vivo and in vitro under stresses including heat, nutrient deprivation and ischemia. Experiments in in vivo models of stroke indicate that transgenically overexpressed or virally delivered HSPs can enhance cell survival, but cannot always reduce lesion size. This study aims to assess the effects of virally delivered HSPs in a rat middle cerebral artery occlusion model of reversible focal cerebral ischemia using noninvasive magnetic resonance imaging. Attenuated herpes simplex virus carrying HSP27, HSP70, or a LacZ control was microinjected into the striatum 3 days before ischemia. Multislice T₂-weighted images at 24 h after ischemia indicated that lesion volume was reduced by 44% in HSP27-treated animals compared with controls (P=0.019). No significant differences were found between HSP70-treated and control animals (P=0.88). Immunohistochemistry and Western blots revealed that HSP27 and HSP70 expression levels were equally high in injected hemispheres, but only the former had an effect on lesion size. This is the first evidence of the efficacy of gene therapy with any viral vector expressing HSP27 in an experimental model of stroke.