Saccular intracranial aneurysm: pathology and mechanisms

Acta Neuropathol. 2012 Jun;123(6):773-86. doi: 10.1007/s00401-011-0939-3. Epub 2012 Jan 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneurysm, Ruptured / etiology
  • Aneurysm, Ruptured / metabolism
  • Aneurysm, Ruptured / pathology*
  • Animals
  • Cerebral Arterial Diseases / etiology
  • Cerebral Arterial Diseases / metabolism
  • Cerebral Arterial Diseases / pathology
  • Humans
  • Inflammation / pathology
  • Intracranial Aneurysm / metabolism
  • Intracranial Aneurysm / pathology*
  • Oxidative Stress
  • Thrombosis / pathology