Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial aneurysm initiation in a rabbit model

J Vasc Res. 2011;48(5):429-42. doi: 10.1159/000324840. Epub 2011 May 31.


Background/aims: Hemodynamics constitute a critical factor in the formation of intracranial aneurysms. However, little is known about how intracranial arteries respond to hemodynamic insult and how that response contributes to aneurysm formation. We examined early cellular responses at rabbit basilar termini exposed to hemodynamic insult that initiates aneurysmal remodeling.

Methods: Flow in the basilar artery was increased by bilateral carotid artery ligation. After 2 and 5 days, basilar terminus tissue was examined by immunohistochemistry and quantitative PCR.

Results: Within 2 days of flow increase, internal elastic lamina (IEL) was lost in the periapical region of the bifurcation, which experienced high wall shear stress and positive wall shear stress gradient. Overlying endothelium was still largely present in this region. IEL loss was associated with localized apoptosis and elevated expression of matrix metalloproteinases (MMPs) 2 and 9. A small number of inflammatory cells were sporadically scattered in the bifurcation adventitia and were not concentrated in regions of IEL loss and MMP elevation. Elevated MMP expression colocalized with smooth muscle α-actin in the media.

Conclusion: The initial vascular response to aneurysm-initiating hemodynamic insult includes localized matrix degradation and cell apoptosis. Such destructive remodeling arises from intrinsic mural cells, rather than through inflammatory cell infiltration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Basilar Artery / physiology*
  • Carotid Arteries / physiology
  • Cerebrovascular Circulation / physiology*
  • Disease Models, Animal
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiology
  • Female
  • Hemodynamics / physiology*
  • Intracranial Aneurysm / pathology*
  • Intracranial Aneurysm / physiopathology*
  • Ligation
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / pathology
  • Rabbits
  • Stress, Mechanical
  • Tunica Media / pathology
  • Tunica Media / physiology


  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9