Neural induction of the blood-brain barrier: Still an enigma

1. The study of the blood-brain barrier and its various realms offers a myr iad of opportunities for scientific exploration. This review focuses on two of these areas in particular: the induction of the blood-brain barrier and the molecular mechanisms underlying this developmental process. 2. The creation of the blood-brain barrier is considered a specific step in the differentiation of cerebral capillary endothelial cells, resulting in a number of biochemical and functional alterations. Although the specific e ndothelial properties which maintain the homeostasis in the central nervous system necessary for neuronal function have been well described, the induc tive mechanisms which trigger blood-brain barrier establishment in capillar y endothelial cells are unknown. 3. The timetable of blood-brain barrier formation is still a matter of deba te, caused largely by the use of varying experimental systems and by the ge neral difficulty of quantitatively measuring the degree of blood-brain barr ier "tightness." However, there is a general consensus that a gradual forma tion of the blood-brain barrier starts shortly after intraneural neovascula rization and that the neural microenvironment (neurons and/or astrocytes) p lays a key role in inducing blood-brain barrier function in capillary endot helial cells. This view stems from numerous in vitro experiments using most ly cocultures of capillary endothelial cells and astrocytes and assays for easily measurable blood-brain barrier markers. In vivo, there are great dif ficulties in proving the inductive influence of the neuronal environment. A lso dealt with in this article are brain tumors, the least understood in vi vo systems, and the induction or noninduction of barrier function in the ne wly established tumor vascularization. 4. Finally, this review tries to elucidate the question concerning the natu re of the inductive signal eliciting blood-brain barrier formation in the c erebral microvasculature.