Differential Interstrain Susceptibility to Vertebrobasilar Dolichoectasia in a Mouse Model

BACKGROUND AND PURPOSE: Vetebrobasilar dolichoectasia is characterized by arterial elongation, dilation, and tortuosity and leads to high risks of ischemic stroke. Our aim was to investigate the differential susceptibility to elastase-induced vertebrobasilar dolichoectasia induction in 2 different mouse strains.

MATERIALS AND METHODS: Elastase (25 mU) was injected into the cisterna magna in C57BL/6J (n = 36) and 129/SvEv (SV129) (n = 36) mice. Control animals were injected with heat-inactivated elastase (n = 12 for each strain). At 3, 7, 14, and 28 days after elastase injection, MICROFIL polymer perfusion was performed. The arterial tortuosity index and the percentage increase in diameter were calculated for the basilar artery. Arterial samples were processed for conventional histologic examination, immunostaining, and matrix metalloproteinase expression. A ≥50% increase in diameter and a tortuosity index of ≥10 for the basilar artery were used to indicate success in achieving vertebrobasilar dolichoectasia.

RESULTS: Successful vertebrobasilar dolichoectasia induction was noted in 67% (18 of 27) of the C57BL/6J strain versus 0% (0 of 19) of the SV129 strain (P < .001). Vertebrobasilar dolichoectasia was not observed in sham-operated controls. Both the tortuosity index and diameter increase for the basilar artery were greater in the C57BL/6J strain compared with the SV129 strain (56.3% ± 16.4% versus 21.1% ± 21.6% for diameter, P < .001; 17.4 ± 7.6 versus 10.4 ± 3.8 for tortuosity index, P < .001). Expression of pro-matrix metalloproteinase-2 and pro- and active matrix metalloproteinase-9 was increased in elastase-injected C57BL/6J animals compared with elastase-injected SV129 animals (P = .029, 0.029, and 0.029, respectively). Inflammation scores were significantly higher in C57BL/6J animals versus SV129 animals (P < .001). C57BL/6J subjects demonstrated arterial wall dilation and elongation characterized by internal elastic lamina disruption, muscular layer discontinuity, inflammatory cell infiltration, and high matrix metalloproteinase expression in the media.

CONCLUSIONS: C57BL/6J mice demonstrated greater susceptibility to vertebrobasilar dolichoectasia induction than SV129 mice.