K L Hallene G Dini and D Janigro

The Cleveland Clinic Foundation, Cleveland, Ohio

The blood-brain barrier (BBB) has been described in detail over the years, both physiologically and morphologically [1]. At the cellular level, the BBB is composed of glia and microvascular endothelial cells (ECs). The latter are characterized by the presence of tight junctions, lack of fenestrations, and minimal pinocytotic vesicles. ECs, together with astrocytes, form a selectively permeable barrier protecting the brain from systemic influences, while still providing pathways of transport for nourishment to neurons in the parenchyma. Today, it is generally accepted that movement of ions and molecules across the BBB is restricted due to endothelial cell tight junctions. However, under certain conditions, some toxins may actually increase BBB permeability, allowing entry of potentially noxious substances into the brain. It is therefore recognized that the blood-brain barrier plays a crucial role in the determination of neurotoxic-ity and its prevention by specific transport mechanisms [2].

Because of the anatomical and topographic obstacles associated with the direct investigation of BBB in vivo, its structure and physiological properties are often inferred from studies of isolated microvessels and primary cultures of brain microvascular endothelial cells. This is true for both the normal and disease states.

Experimental observations first made over a century ago showed that the central nervous system (CNS) is not stained by intravascular water-soluble dyes, providing the first demonstration of the existence of a barrier to the passage of polar compounds from the blood to the brain. pioneering studies of the BBB were performed in vivo using intrac-arotid injection single-pass techniques. Further characterization of the BBB at the cellular level more recently has led to the development of in vitro experimental approaches. Isolated brain microvasculature preparations, as well as tissue culture systems using brain endothelial cells, have proven to be a promising methodology to define the characteristics of the brain capillary endothelium at the molecular and cellular level. The purpose of this review is to describe the virtues and pitfalls of cell culture-based models of the BBB.

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