title: A fibre matrix model for the restricting junction of the blood-brain barrier in a cephalopod mollusc: implications for capillary and epithelial permeability.
abstract: A model is proposed for the novel restricting junction forming the blood-brain barrier in a cephalopod mollusc, the cuttlefish Sepia officinalis. The model is based on electron-microscopic findings, from both thin-section and freeze-fracture material, the distribution of electron-dense tracers, and radioisotopic measurements of permeability using small non-electrolytes. Biochemical properties of Sepia plasma proteins are also considered. It is proposed that an effective blood-brain barrier is achieved by a combination of mechanisms. As much as 90% of the Sepia brain microvessel wall is covered by a 'seamless' glial sheath, without intercellular clefts, limiting the number of potential leakage sites. The remaining clefts follow a tortuous course increasing the diffusion path to the neuropile. Entry into the clefts is reduced by a restricting junctional region at the luminal end, characterized by delicate striations spanning the cleft, and forming an effective barrier to both horseradish peroxidase and ionic lanthanum. This is a novel junctional type, different from previously-described vertebrate and invertebrate occluding junctions. It is proposed that the junction acts as a fine-mesh molecular filter, with condensed extracellular material in the cleft, cross-linked and consolidated by bound plasma protein. Cephalopod haemocyanin or its subcomponents are considered likely candidates for the bound protein. The model predicts that blood-brain barrier permeability should be sensitive to the charge structure of the extracellular matrix and the presence of protein, and is analogous to the 'fibre matrix' model of vertebrate capillary permeability. The Sepia blood-brain barrier also highlights the different strategies available for constructing a restricting cell layer, and suggests a possible evolutionary pattern underlying the present range of junctional mechanisms in vertebrate and invertebrate epithelia.
authors.affiliation: Biomedical Sciences Division, King's College, London University, Strand, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Abbott
authors.forename: N J
authors.initials: NJ
authors.lastname: Lane
authors.forename: M
authors.initials: M
authors.lastname: Bundgaard
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D002199:Capillary Permeability; D002463:Cell Membrane Permeability; D004848:Epithelium / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008974:Mollusca / Q000648:ultrastructure*