title: APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.
abstract: Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.
authors.affiliation: Wellcome Surgical Institute, Division of Clinical Neuroscience, University of Glasgow, Garscube Estate, Glasgow, UK.
authors.forename: Barry W
authors.initials: BW
authors.lastname: McColl
authors.forename: Ailsa L
authors.initials: AL
authors.lastname: McGregor
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.forename: Julian D
authors.initials: JD
authors.lastname: Harris
authors.forename: Andrea
authors.initials: A
authors.lastname: Amalfitano
authors.forename: Sandra
authors.initials: S
authors.lastname: Magnoni
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
authors.forename: George
authors.initials: G
authors.lastname: Dickson
authors.forename: Karen
authors.initials: K
authors.lastname: Horsburgh
mesh_terms: D000256:Adenoviridae; D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D020521:Stroke / Q000473:pathology / Q000628:therapy*
chemical_list: D053318:Apolipoprotein E3; D049452:Green Fluorescent Proteins