title: Induction of Genes Expressed in Endothelial Cells of the Corpus Callosum in the Chronic Cerebral Hypoperfusion Rat Model.
abstract: BACKGROUND
  Cerebrovascular white matter lesions (WMLs) are associated with cognitive impairment in patients with subcortical vascular dementia. We performed a comprehensive gene expression analysis to elucidate genes associated with WML development in a chronic cerebral hypoperfusion rat model.
  
  
  METHODS
  Brains of rats with bilateral carotid ligation (2VO, n = 10) and sham-operated rats (n = 5-10/group) were removed on days 1, 7, or 28 after surgery. Total RNA isolated from the corpus callosum was evaluated by microarray analysis and quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  On days 7 and 28, WMLs exhibited histologic changes. On day 7, 16 genes were differentially expressed between groups. mRNA levels of Ptprb, Kcnj8, Crispld2, Bcl6b, and Gja5 were differentially expressed in 2VO rats on day 7, but then returned to normal, whereas mRNA levels of Vwf and Trappc6a were upregulated after day 7. Immunohistochemistry showed that GJA5 and vWF were detected in endothelial cells, KCNJ8 in endothelial cells and astrocytes, CRISPLD2 in neurons and astrocytes, and TRAPPC6A in neurons.
  
  
  CONCLUSIONS
  Our findings indicate novel genes that may be associated with WML development in the chronic cerebral hypoperfusion rat model, and suggest an important role of neurovascular dysfunction in the pathophysiology.
authors.affiliation: Department of Neurology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Aso
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemaru
authors.forename: Ryuki
authors.initials: R
authors.lastname: Arakawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujiki
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Hirano
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002908:Chronic Disease; D003337:Corpus Callosum / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D066127:White Matter / Q000473:pathology*