Neuroprotective effects of virally delivered HSPs in experimental stroke.
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 T(2)-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.
Badin
Romina Aron
RA
RCS Unit of Biophysics, Institute of Child Health, University College London, UK. R.Aron-Badin@ich.ucl.ac.uk
Lythgoe
Mark F
MF
van der Weerd
Louise
L
Thomas
David L
DL
Gadian
David G
DG
Latchman
David S
DS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D018139:Simplexvirus / Q000235:genetics; D020521:Stroke / Q000378:metabolism / Q000628:therapy* / Q000821:virology
D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents