title: Drug-induced changes to the vertebral endplate vasculature affect transport into the intervertebral disc in vivo.
abstract: Intervertebral disc health is mediated in part by nutrient diffusion from the microvasculature in the adjacent subchondral bone. Evidence suggests that a reduction in nutrient diffusion contributes to disc degeneration, but the role of the microvasculature is unclear. The purpose of this study was to induce changes in the endplate microvasculature in vivo via pharmaceutical intervention and then correlate microvasculature characteristics to diffusion and disc health. New Zealand white rabbits were administered either nimodipine (to enhance microvessel density) or nicotine (to diminish microvessel density) daily for 8 weeks compared to controls. Trans-endplate diffusion and disc health were quantified using post-contrast enhanced magnetic resonance imaging (MRI). Histology was utilized to assess changes to the subchondral vasculature. Results indicate that nimodipine increased vessel area and vessel-endplate contact length, causing a significant increase in disc diffusion. Surprisingly, nicotine caused increases in vessel number and area but did not alter diffusion into the disc. The drug treatments did affect the microvasculature and diffusion, but the relationship between the two is complex and dependent on multiple factors which include vessel-endplate distance, and vessel-endplate contact length in addition to vessel density. Our data suggest that drugs can modulate these factors to augment or diminish small molecule transport.
authors.affiliation: Department of Biomedical Engineering, Rensselear Polytechnic Institute, JEC 7044, 110 8th Street, Troy, New York 1280.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gullbrand
authors.forename: Joshua
authors.initials: J
authors.lastname: Peterson
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mastropolo
authors.forename: James P
authors.initials: JP
authors.lastname: Lawrence
authors.forename: Luciana
authors.initials: L
authors.lastname: Lopes
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lotz
authors.forename: Eric H
authors.initials: EH
authors.lastname: Ledet
mesh_terms: D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D007403:Intervertebral Disc / Q000098:blood supply / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D055806:Microvessels / Q000187:drug effects; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D009553:Nimodipine / Q000097:blood / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D009553:Nimodipine; D009538:Nicotine
keywords: diffusion; intervertebral disc; microvasculature; vertebral endplate