title: Oxidative stress is associated with cell death, wall degradation, and increased risk of rupture of the intracranial aneurysm wall.
abstract: BACKGROUND
  The cause of rupture of intracranial aneurysms (IA) is not well understood. We previously demonstrated that loss of cells from the IA wall is associated with wall degeneration and rupture.
  
  
  OBJECTIVE
  To investigate the mechanisms mediating cell death in the IA wall.
  
  
  METHODS
  Snap-frozen tissue samples from aneurysm fundi were studied with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunostaining (14 unruptured and 20 ruptured), as well as with Western blot (12 unruptured and 12 ruptured).
  
  
  RESULTS
  : Ruptured IA walls had more TUNEL-positive cells than unruptured walls (P < .001). Few cells positive for cleaved caspase-3 were detected. Cleaved caspase-9 (intrinsic activation of apoptosis) was significantly increased in ruptured IA walls, whereas cleaved caspase-8 (extrinsic activation of apoptosis) was not detected. Increased expression of hemeoxygenase-1, a marker for oxidative stress, was associated with IA wall degeneration and rupture.
  
  
  CONCLUSIONS
  Our results show that programmed cell death is activated in the IA wall via the intrinsic pathway. High oxidative stress in the IA wall is probably a significant cause of the intrinsic activation of cell death.
authors.affiliation: Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Laaksamo
authors.forename: Riikka
authors.initials: R
authors.lastname: Tulamo
authors.forename: Arto
authors.initials: A
authors.lastname: Liiman
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friedlander
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Marko
authors.initials: M
authors.lastname: Kangasniemi
authors.forename: Mika
authors.initials: M
authors.lastname: Niemelä
authors.forename: Aki
authors.initials: A
authors.lastname: Laakso
authors.forename: Juhana
authors.initials: J
authors.lastname: Frösen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000473:pathology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002532:Intracranial Aneurysm / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D018384:Oxidative Stress / Q000502:physiology*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013345:Subarachnoid Hemorrhage / Q000473:pathology
chemical_list: D051547:Heme Oxygenase-1; D053148:Caspase 3; D053453:Caspase 9