Ultrastructure of the blood-brain barrier in the rabbit

The morphology of the normal blood-brain barrier in the rabbit by thin sect ion and freeze-fracture electron microscopy is reported. Exogenous tracer h orseradish peroxidase was injected to visualize the integrity of the blood- brain barrier in New Zealand White rabbits. Freeze-fracture was used to det ermine the intramembrane architecture of the tight junctions. Thin sections (60-100 nm) of brain capillaries from animals injected with horseradish pe roxidase (HRP) possessed few pinocytotic vesicles in the cytoplasm. Junctio nal profiles between adjoining plasma membranes were present. Thin sections of capillaries containing electron dense HRP reaction product (HRP-RP) in the lumen revealed focal fusions of apposing plasma membranes that occluded reaction product from entering the junctional clefts. Some cytoplasmic ves icles were filled with HRP-RP; however, basal laminae and brain interstitiu m were free of HRP-RP in all vessel profiles examined. Freeze-fracture elec tron microscopy revealed tight junctions as an elaborate network of interco nnecting strands of intramembrane particles appearing as ridges on the EF f ace and corresponding grooves on the PF face on platinum replicas. Results of this study demonstrate the architecture of rabbit brain microvessel endo thelial junctions (blood-brain barrier) and provide evidence that the tight junctions prevent HRP extravasation. It is concluded that rabbit brain end othelial tight junctions (zonulae occludentes), as in other mammals, form t he anatomical basis of the blood-brain barrier. Consequently, the rabbit br ain microvasculature can be a useful model for establishing stereotactic ra diosurgical procedures to treat brain astrocytomas (tumours).