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  • Drug-induced changes to the vertebral endplate vasculature affect transport into the intervertebral disc in vivo.

Drug-induced changes to the vertebral endplate vasculature affect transport into the intervertebral disc in vivo.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2014-09-05)
Sarah E Gullbrand, Joshua Peterson, Rosemarie Mastropolo, James P Lawrence, Luciana Lopes, Jeffrey Lotz, Eric H Ledet
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Formaldehyde-12C solution, 20% in H2O, 99.9 atom % 12C
Sigma-Aldrich
Formaldehyde solution, tested according to Ph. Eur.
Sigma-Aldrich
Formaldehyde solution, Molecular Biology, BioReagent, ≥36.0% in H2O (T)
Supelco
(−)-Nicotine, PESTANAL®, analytical standard
Sigma-Aldrich
Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
Sigma-Aldrich
(−)-Nicotine, ≥99% (GC), liquid
Supelco
Formaldehyde solution, stabilized with methanol, ~37 wt. % in H2O, certified reference material
Sigma-Aldrich
Formaldehyde solution, Molecular Biology, 36.5-38% in H2O
Supelco
(−)-Nicotine solution, 1.0 mg/mL, analytical standard, for drug analysis
Sigma-Aldrich
Formaldehyde solution, meets analytical specification of USP, ≥34.5 wt. %
SAFC
Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
Sigma-Aldrich
Nimodipine
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, ACS reagent, ≥99.5%
Supelco
Nimodipine, Pharmaceutical Secondary Standard; Certified Reference Material
Nimodipine, European Pharmacopoeia (EP) Reference Standard
Supelco
S(−)-Nicotine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®