Ultrastructure of the blood-brain barrier in the rabbit

Abstract

The morphology of the normal blood-brain barrier in the rabbit by thin section and freeze-fracture electron microscopy is reported. Exogenous tracer horseradish peroxidase was injected to visualize the integrity of the blood-brain barrier in New Zealand White rabbits. Freeze-fracture was used to determine the intramembrane architecture of the tight junctions. Thin sections (60-100 nm) of brain capillaries from animals injected with horseradish peroxidase (HRP) possessed few pinocytotic vesicles in the cytoplasm. Junctional 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 vesicles were filled with HRP-RP; however, basal laminae and brain interstitium were free of HRP-RP in all vessel profiles examined. Freeze-fracture electron microscopy revealed tight junctions as an elaborate network of interconnecting strands of intramembrane particles appearing as ridges on the EF face and corresponding grooves on the PF face on platinum replicas. Results of this study demonstrate the architecture of rabbit brain microvessel endothelial junctions (blood-brain barrier) and provide evidence that the tight junctions prevent HRP extravasation. It is concluded that rabbit brain endothelial tight junctions (zonulae occludentes), as in other mammals, form the anatomical basis of the blood-brain barrier. Consequently, the rabbit brain microvasculature can be a useful model for establishing stereotactic radiosurgical procedures to treat brain astrocytomas (tumours).