Progressive aneurysm development following hemodynamic insult

Laboratory investigation

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Object

Hemodynamic insult has been speculated to be a key factor in intracranial aneurysm formation; however, it is unclear whether a sustained insult is necessary. The authors examined whether aneurysmal degradation would continue despite the normalization of wall shear stress (WSS) by adaptive outward vascular remodeling.

Methods

Twenty-five rabbits underwent either sham operation (5 animals) or bilateral common carotid artery ligation (20 animals) to augment basilar artery (BA) flow. Basilar termini (BTs) were harvested at 5 days and 3, 12, and 27 weeks postoperation. Histological changes at the BTs were quantified using an aneurysm development score (ADS) wherein the luminal length of the vessel wall exhibiting internal elastic lamina (IEL) loss, media thinning (> 30% media loss), and bulging was multiplied by the percentage of media thinning divided by the BA diameter. This score and its component variables were evaluated over the specified time points and compared with the WSS time course obtained from multiple angiography and BA flow velocity measurements.

Results

Serial examination of histological sections from the ligation group (17 rabbits survived the procedure) demonstrated localized, progressive, degenerative, and aneurysmal changes at the BTs. Prominent IEL loss was observed in BT specimens from all ligated animals. Media thinning and luminal bulging significantly progressed over the 27-week follow-up. The composite ADS significantly increased over the study period, indicating progressive aneurysm development, although the WSS returned to preligation baseline values within 5 weeks of ligation.

Conclusions

Hemodynamic insult can elicit a pathological vascular response leading to a self-sustaining aneurysmal remodeling that does not require persistence of the original inciting factor to continue its pathological progression.

Abbreviations used in this paper: ADS = aneurysm development score; BA = basilar artery; BT = basilar terminus; CCA = common carotid artery; CFD = computational fluid dynamics; IA = intracranial aneurysm; IEL = internal elastic lamina; SMC = smooth-muscle cell; TCD = transcranial Doppler; WSS = wall shear stress; WSSG = WSS gradient.
Article Information

Contributor Notes

Address correspondence to: Hui Meng, Ph.D., Toshiba Stroke Research Center, University at Buffalo, The State University of New York, 447 Biomedical Research Building, 3435 Main Street, Buffalo, New York 14214. email: huimeng@buffalo.edu.Please include this information when citing this paper: published online October 15, 2010; DOI: 10.3171/2010.9.JNS10368.
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