title: Ischemic blood-brain barrier and amyloid in white matter as etiological factors in leukoaraiosis.
abstract: BACKGROUND
  Pathology of white matter, which is observed in ischemic brain, indicates that similar processes contribute to Alzheimer's disease development. These injuries have been seen in the subcortical and periventricular regions. Periventricular white matter changes in ischemic and Alzheimer's disease brain, referred to as leukoaraiosis, are responsible for changes in memory, cognition and behavior. It is not clear whether the blood-brain barrier in ischemic periventricular white matter is altered in aged animals.
  
  
  METHODS
  We studied blood-brain barrier changes with amyloid precursor protein staining around blood-brain barrier vessels. Rats were made ischemic by cardiac arrest. Blood-brain barrier insufficiency, accumulation of amyloid precursor protein and platelets around blood-brain barrier vessels were investigated in ischemic periventricular white matter up to 1-year survival.
  
  
  RESULTS
  Ischemic periventricualr white matter demonstrated enduring blood-brain barrier changes. Toxic fragments of amyloid precursor protein deposits were associated with the blood-brain barrier vessels. Moreover our investigation revealed platelet aggregates in- and outside blood-brain barrier vessels. Toxic parts of amyloid precursor protein and platelet aggregates correlated very well with blood-brain barrier permeability.
  
  
  CONCLUSIONS
  Progressive injury of the ischemic periventricular white matter may be caused not only by a degeneration of neurons destroyed during ischemia but also by damage in blood-brain barrier. Chronic ischemic blood-brain barrier insufficiency with accumulation of toxic components of amyloid precursor protein in the periventricular white matter perivascular space, may gradually over a lifetime, progress to leukoaraiosis and finally to severe dementia.
authors.affiliation: Laboratory of Ischemic and Neurodegenerative Brain Research, Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 Str, 02-106 Warsaw, Poland. pluta@cmdik.pan.pl
authors.forename: Ryszard
authors.initials: R
authors.lastname: Pluta
authors.forename: Sławomir
authors.initials: S
authors.lastname: Januszewski
authors.forename: Marzena
authors.initials: M
authors.lastname: Ułamek
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006323:Heart Arrest / Q000150:complications; D006735:Horseradish Peroxidase; D007511:Ischemia / Q000209:etiology / Q000473:pathology*; D049292:Leukoaraiosis / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006735:Horseradish Peroxidase