title: AAV-mediated targeting of gene expression to the peri-infarct region in rat cortical stroke model.
abstract: BACKGROUND
  For stroke patients the recovery of cognitive and behavioral functions is often incomplete. Functional recovery is thought to be mediated largely by connectivity rearrangements in the peri-infarct region. A method for manipulating gene expression in this region would be useful for identifying new recovery-enhancing treatments.
  
  
  METHODS
  We have characterized a way of targeting adeno-associated virus (AAV) vectors to the peri-infarct region of cortical ischemic lesion in rats 2days after middle cerebral artery occlusion (MCAo).
  
  
  RESULTS
  We used magnetic resonance imaging (MRI) to show that the altered properties of post-ischemic brain tissue facilitate the spreading of intrastriatally injected nanoparticles toward the infarct. We show that subcortical injection of green fluorescent protein-encoding dsAAV7-GFP resulted in transduction of cells in and around the white matter tract underlying the lesion, and in the cortex proximal to the lesion. A similar result was achieved with dsAAV7 vector encoding the cerebral dopamine neurotrophic factor (CDNF), a protein with therapeutic potential.
  
  
  METHODS
  Viral vector-mediated intracerebral gene delivery has been used before in rodent models of ischemic injury. However, the method of targeting gene expression to the peri-infarct region, after the initial phase of ischemic cell death, has not been described before.
  
  
  CONCLUSIONS
  We demonstrate a straightforward and robust way to target AAV vector-mediated over-expression of genes to the peri-infarct region in a rat stroke model. This method will be useful for studying the action of specific proteins in peri-infarct region during the recovery process.
authors.affiliation: Institute of Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Kert
authors.initials: K
authors.lastname: Mätlik
authors.affiliation: Institute of Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Usama
authors.initials: U
authors.lastname: Abo-Ramadan
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.affiliation: Institute of Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland; Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.
authors.forename: Urmas
authors.initials: U
authors.lastname: Arumäe
authors.affiliation: Institute of Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland. Electronic address: mikko.airavaara@helsinki.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Airavaara
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy / Q000821:virology; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy / Q000821:virology; D014161:Transduction, Genetic / Q000379:methods
chemical_list: C577430:CDNF protein, rat; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins
keywords: Adeno-associated virus; Animal models; Focal ischemia; Functional recovery; Gene transfer; Peri-infarct region