Role of apoptosis in intracranial aneurysm rupture

J Neurosurg. 2004 Dec;101(6):1018-25. doi: 10.3171/jns.2004.101.6.1018.


Object: Mechanisms involved in the rupture of intracranial aneurysms remain unclear, and the literature on apoptosis in these lesions is extremely limited. The hypothesis that apoptosis may reduce aneurysm wall resistance, thus contributing to its rupture, warrants investigation. The authors in this study focused on the comparative evaluation of apoptosis in ruptured and unruptured intracranial aneurysms. Peripheral arteries in patients harboring the aneurysms and in a group of controls were also analyzed.

Methods: Between September 1999 and February 2002, specimens from 27 intracranial aneurysms were studied. In 13 of these patients apoptosis was also evaluated in specimens of the middle meningeal artery (MMA) and the superficial temporal artery (STA). The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique was used to study apoptosis via optical microscopy; electron microscopy evaluation was performed as well. Apoptotic cell levels were related to patient age and sex, aneurysm volume and shape, and surgical timing. Significant differences in apoptosis were observed when comparing ruptured and unruptured aneurysms. High levels of apoptosis were found in 88% of ruptured aneurysms and in only 10% of unruptured lesions (p < 0.001). Elevated apoptosis levels were also detected in all MMA and STA specimens obtained in patients harboring ruptured aneurysms, whereas absent or very low apoptosis levels were observed in MMA and STA specimens from patients with unruptured aneurysms. A significant correlation between aneurysm shape and apoptosis was found.

Conclusions: In this series, aneurysm rupture appeared to be more related to elevated apoptosis levels than to the volume of the aneurysm sac. Data in this study could open the field to investigations clarifying the causes of aneurysm enlargement and rupture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aneurysm, Ruptured / pathology*
  • Apoptosis*
  • Cerebral Arteries / pathology
  • Cerebral Arteries / ultrastructure
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Intracranial Aneurysm / pathology*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Subarachnoid Hemorrhage / pathology*