title: Differential Interstrain Susceptibility to Vertebrobasilar Dolichoectasia in a Mouse Model.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  C57BL/6J mice demonstrated greater susceptibility to vertebrobasilar dolichoectasia induction than SV129 mice.
authors.affiliation: From the Department of Radiology (Y.-Q.Z., H.X., D.D., D.F.K., R.K.), Mayo Clinic, Rochester, Minnesota.|Department of Radiology (Y.-Q.Z.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Y-Q
authors.identifier: 0000-0001-5476-9075
authors.initials: YQ
authors.lastname: Zhu
authors.affiliation: From the Department of Radiology (Y.-Q.Z., H.X., D.D., D.F.K., R.K.), Mayo Clinic, Rochester, Minnesota.|Department of Pathology (H.X.), Shanghai East Hospital, Medical School of Shanghai Tongji University, Shanghai, China.
authors.forename: H
authors.identifier: 0000-0002-5906-9657
authors.initials: H
authors.lastname: Xing
authors.affiliation: From the Department of Radiology (Y.-Q.Z., H.X., D.D., D.F.K., R.K.), Mayo Clinic, Rochester, Minnesota.
authors.forename: D
authors.identifier: 0000-0003-4051-6450
authors.initials: D
authors.lastname: Dai
authors.affiliation: From the Department of Radiology (Y.-Q.Z., H.X., D.D., D.F.K., R.K.), Mayo Clinic, Rochester, Minnesota.
authors.forename: D F
authors.identifier: 0000-0002-8495-0040
authors.initials: DF
authors.lastname: Kallmes
authors.affiliation: From the Department of Radiology (Y.-Q.Z., H.X., D.D., D.F.K., R.K.), Mayo Clinic, Rochester, Minnesota kadir@mayo.edu.
authors.forename: R
authors.identifier: 0000-0002-6786-9953
authors.initials: R
authors.lastname: Kadirvel
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000473:pathology; D002946:Cisterna Magna; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010196:Pancreatic Elastase; D013045:Species Specificity; D014715:Vertebrobasilar Insufficiency / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D010196:Pancreatic Elastase; D020782:Matrix Metalloproteinases