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Saccular intracranial aneurysm: pathology and mechanisms

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Abstract

Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a reaction to the ongoing degenerative processes, rather than the cause. Current data suggest that the loss of mural cells and wall degeneration are related to impaired endothelial function and high oxidative stress, caused in part by luminal thrombosis. The aberrant flow conditions caused by sIA geometry are the likely cause of the endothelial dysfunction, which results in accumulation of cytotoxic and pro-inflammatory substances into the sIA wall, as well as thrombus formation. This may start the processes that eventually can lead to the decellularized and degenerated sIA wall that is prone to rupture.

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Acknowledgments

This work was supported by the research funds of The Helsinki University Central Hospital (EVO Grant TYH 2010209) and research grants from The Sigrid Juselius Foundation, Helsinki, Finland; The Maire Taponen Foundation, Helsinki, Finland; and The Biomedicum Helsinki Foundation, Helsinki, Finland.

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  1. Department of Neurosurgery, Helsinki University Central Hospital, Topeliuksenkatu 5, 00260, Helsinki, Finland

    Juhana Frösen, Miikka Korja, Aki Laakso, Mika Niemelä & Juha Hernesniemi

  2. Neurosurgery Research Group, Biomedicum Helsinki, Helsinki, Finland

    Juhana Frösen, Riikka Tulamo, Elisa Laaksamo, Miikka Korja, Aki Laakso, Mika Niemelä & Juha Hernesniemi

  3. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

    Anders Paetau

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Frösen, J., Tulamo, R., Paetau, A. et al. Saccular intracranial aneurysm: pathology and mechanisms. Acta Neuropathol 123, 773–786 (2012). https://doi.org/10.1007/s00401-011-0939-3

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