title: A failure of matrix metalloproteinase inhibition in the prevention of rat intracranial aneurysm formation.
abstract: We tested the hypothesis that nonspecific matrix metalloproteinase (MMP) inhibition with doxycycline would decrease the incidence of intracranial aneurysm formation in a rat aneurysm model. We performed common carotid artery ligation on 96 Long-Evans rats. A treatment group of 48 animals was chosen at random to receive oral doxycycline (3 mg/kg) in addition to standard rat chow, and the control group of 48 animals received standard rat chow only. The major circle of Willis arteries was dissected at 1 year following carotid ligation, and the proportions of animals with aneurysms were compared between groups using Fisher's exact test. Four animals given oral doxycycline and ten control animals expired before 1 year. Of the examined animals, eight saccular intracranial aneurysms were found in 8 of 45 animals which had received doxycycline (17.8%) and seven saccular intracranial aneurysms were found in 7 of 37 control animals (18.9%). There was no significant difference in aneurysm formation between the doxycycline-treated and control groups (P=0.894). Nonspecific MMP inhibition with doxycycline is not effective in preventing intracranial aneurysm formation in a rat model.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Mayo Building, E2, Rochester, MN 55905, USA. kaufmann.timothy@mayo.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Kaufmann
authors.forename: W F
authors.initials: WF
authors.lastname: Marx
authors.forename: D F
authors.initials: DF
authors.lastname: Kallmes
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common / Q000601:surgery; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D002532:Intracranial Aneurysm / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008026:Ligation; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D020318:Rats, Long-Evans; D017211:Treatment Failure
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline