title: Inhibition of vertebral endplate perfusion results in decreased intervertebral disc intranuclear diffusive transport.
abstract: Impaired nutrition of the intervertebral disc has been hypothesized to be one of the causes of disc degeneration. However, no causal relationship between decreased endplate perfusion and limited nutrient transport has been demonstrated to support this pathogenic mechanism. To determine the importance of endplate perfusion on solute diffusion into the nucleus pulposus and to show causality of endplate perfusion on intranuclear diffusion in large animal lumbar intervertebral discs, diffusive transport into ovine lumbar intervertebral discs was evaluated after inhibiting adjacent vertebral endplate perfusion. Partial perfusion blocks were created in vertebrae close and parallel to both endplates of lumbar discs of anaesthetized sheep. To assess diffusivity of small molecules through the endplate, N2O was introduced into the inhalation gas mixture and concentrations of intranuclear N2O were measured for 35 min thereafter. Post mortem, procion red was infused through the spinal vasculature and perfusion through the endplate was assessed by quantifying the density of dye-perfused endplate vascular buds in histology sections. Perfusion of the endplates overlying the nucleus pulposus was inhibited by almost 50% in the partially blocked discs relative to the control discs. There was also a nine-fold decreased transport rate of intranuclear N2O in partially blocked discs compared with control discs. The density of perfused endplate vascular buds correlated significantly to the amount of transported intranuclear N2O (r2 = 0.52, P = 0.008). The vertebral endplate was demonstrated to be the main route of intravascular solute transport into the nucleus pulposus of intervertebral discs, and inhibition of endplate perfusion can cause inhibited solute transport into the disc intranuclear tissue.
authors.affiliation: AO Research Institute, Davos, Switzerland.
authors.forename: Marije
authors.initials: M
authors.lastname: van der Werf
authors.forename: Patrick
authors.initials: P
authors.lastname: Lezuo
authors.forename: Otto
authors.initials: O
authors.lastname: Maissen
authors.forename: Corrinus C
authors.initials: CC
authors.lastname: van Donkelaar
authors.forename: Keita
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D006132:Growth Plate / Q000378:metabolism* / Q000473:pathology; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae; D023421:Models, Animal; D009585:Nitrogen Dioxide / Q000493:pharmacokinetics*; D010477:Perfusion; D012756:Sheep; D013122:Spinal Diseases / Q000209:etiology / Q000473:pathology
chemical_list: D009585:Nitrogen Dioxide