APOE ε3 gene transfer attenuates brain damage after experimental stroke

Barry W. McColl, Ailsa L. McGregor, Andrew Wong, Julian D. Harris, Andrea Amalfitano, Sandra Magnoni, Andrew H. Baker, George Dickson, Karen Horsburgh

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 ε3 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 ε3 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 mm3). 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.

Original languageEnglish
Pages (from-to)477-487
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 14 2007

Fingerprint

Apolipoproteins E
Stroke
Brain
Genes
Green Fluorescent Proteins
Transient Ischemic Attack
Therapeutics
Brain Ischemia
Brain Injuries
Carrier Proteins
Ischemia
Lipids
Gene Expression
Injections
Proteins

Keywords

  • Adenovirus
  • Apolipoprotein E
  • Cerebral ischaemia
  • Gene therapy
  • Neuroprotection

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

McColl, B. W., McGregor, A. L., Wong, A., Harris, J. D., Amalfitano, A., Magnoni, S., ... Horsburgh, K. (2007). APOE ε3 gene transfer attenuates brain damage after experimental stroke. Journal of Cerebral Blood Flow and Metabolism, 27(3), 477-487. https://doi.org/10.1038/sj.jcbfm.9600361

APOE ε3 gene transfer attenuates brain damage after experimental stroke. / McColl, Barry W.; McGregor, Ailsa L.; Wong, Andrew; Harris, Julian D.; Amalfitano, Andrea; Magnoni, Sandra; Baker, Andrew H.; Dickson, George; Horsburgh, Karen.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. 3, 14.03.2007, p. 477-487.

Research output: Contribution to journalArticle

McColl, BW, McGregor, AL, Wong, A, Harris, JD, Amalfitano, A, Magnoni, S, Baker, AH, Dickson, G & Horsburgh, K 2007, 'APOE ε3 gene transfer attenuates brain damage after experimental stroke', Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 3, pp. 477-487. https://doi.org/10.1038/sj.jcbfm.9600361
McColl BW, McGregor AL, Wong A, Harris JD, Amalfitano A, Magnoni S et al. APOE ε3 gene transfer attenuates brain damage after experimental stroke. Journal of Cerebral Blood Flow and Metabolism. 2007 Mar 14;27(3):477-487. https://doi.org/10.1038/sj.jcbfm.9600361
McColl, Barry W. ; McGregor, Ailsa L. ; Wong, Andrew ; Harris, Julian D. ; Amalfitano, Andrea ; Magnoni, Sandra ; Baker, Andrew H. ; Dickson, George ; Horsburgh, Karen. / APOE ε3 gene transfer attenuates brain damage after experimental stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. 3. pp. 477-487.
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