• Elisa Laaksamo, Riikka Tulamo, Arto Liiman, Marc Baumann, Robert M Friedlander, Juha Hernesniemi, Marko Kangasniemi, Mika Niemelä, Aki Laakso, and Juhana Frösen.
• Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
• Neurosurgery. 2013 Jan 1;72(1):109-17.

BackgroundThe 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.ObjectiveTo investigate the mechanisms mediating cell death in the IA wall.MethodsSnap-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.ConclusionOur 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.

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