Nascent aneurysm formation at the basilar terminus induced by hemodynamics

Abstract

Background and purpose: Hemodynamic insults at arterial bifurcations are hypothesized to play a key role in intracranial aneurysm formation. This study investigates aneurysm-initiating vascular responses at the rabbit basilar terminus subsequent to common carotid artery ligation.

Methods: Nine adult female New Zealand white rabbits were subjected to sham, unilateral, or bilateral common carotid artery ligation to produce varying degrees of compensatory basilar artery flow increase. Basilar artery flow velocity and geometry were monitored by transcranial Doppler and rotational angiography, respectively, for 12 weeks after surgery. Bifurcation tissues were harvested at 12 weeks and examined histologically. From the histological sections, we quantified the destructive structural changes at the basilar terminus and correlated them with the basilar artery flow rate increase.

Results: Subsequent to common carotid artery ligation, basilar artery flow rate increased by 105% to 900% at the maximum. All common carotid artery-ligated rabbits presented nascent aneurysm formation characterized by a bulge with thinned media and absent internal elastic lamina near the basilar terminus. We defined a nascent aneurysm index based on a multiplicative combination of the local destructive remodeling lengths measured at the nascent aneurysm. The nascent aneurysm index strongly correlated with the increase in basilar artery flow rate with R(2)=0.91.

Conclusions: Without other known predisposition, flow increase alone at the basilar bifurcation can lead to a nascent aneurysm. This nascent aneurysm formation is dose-dependent on basilar artery flow increase.

Figure 1

Schematic diagram for nascent aneurysm induction at rabbit BT through CCA ligation. RCCA indicates right CCA; BA, basilar artery; LCCA, left CCA. In the unilateral ligation group, LCCA was left open.

Figure 2

BA flow rate increase postprocedure. A, Flow rate increase over time in individual rabbits. B, Maximum flow rate increase and corresponding baseline flow rate for individual rabbits. Number of days to achieve maximum flow rate increase is indicated in parentheses.

Figure 3

Nascent aneurysm morphology at BT at 84 days (12 weeks) postprocedure. The second and third columns show higher magnification of the apex at the BT. Top row (A1-A3), sham control (rabbit S1). Continuous IEL (purple arrow in A1 and A2) and intact media (between purple arrowheads in A3) are observed. Second row (B1-B3), unilateral ligation (rabbit U2). Bottom row, bilateral ligation (rabbit B3). The ligation groups exhibit loss of IEL (between red arrows in B1 and C1) and thinned media (between red arrowheads in B3 and C3). A1-A2, B1-B2, and C1-C2, Van Gieson staining showing elastin. A3, B3, and C3, trichrome staining showing collagen and cells. Bar=50 μm. L indicates lumen. B=Bulge.

Figure 4

A, Individual maximum destruction lengths at BT, normalized by the rabbit BA diameter, versus maximum BA flow rate increase in the ligated rabbits. B, NAI, a composite that measures the degree of destructive remodeling, shows strong correlation with percentage of BA flow rate increase.