ABSTRACT
INTRODUCTION This review will discuss the evidence explaining which blood-brain barrier mechanisms in the immature brain appear to be functional in relation to what is known about effects of neurotoxic agents in the fetus and newborn. The infl uence of neurotoxic agents on specifi c aspects of brain development have been reviewed in detail elsewhere ( 1-3 ) and will only be dealt with in outline here. There is a widespread belief amongst toxicologists (1,4-13) and neurobiologists ( 14-18 ) that “the” blood-brain barrier in the fetus and newborn is immature or even absent (3) . This appears to be partly due to a teleological view that the developing brain would not “need” a specialized local environment for its development or if it does then this would be supplied by protective functions of the placenta (19) . A more recent but similarly teleological view is that “the rapid growth of the cerebral cortex perhaps necessitates a ‘leaky’ structure of the bloodbrain barrier to accommodate the high demand of blood-borne nutrients for brain growth” (20) . The belief in the immaturity of the blood-brain barrier is often stated without citing evidence, or supported by uncritical acceptance and interpretation of results of three types of experiments. One involves the injection of large volumes or concentrations of barrier markers into fragile embryos or fetuses (21) . The second, which is more directly relevant to toxicological studies, is the interpretation of differences in responses of the brains of adult and immature animals to drugs and toxins as due to barrier immaturity (22) . The third type of experiment is measurement of entry of biologically important molecules such as amino acids into the developing brain. These show unequivocally that the level of transfer is generally greater in the developing rather than in the adult brain (reviewed below). Some have interpreted this as evidence of a “leaky” barrier ( 20 , 23 ). Most of those who did the actual experiments concluded that the greater transfer was a refl ection of a developmental specialization during brain growth ( 24 , 25 ).
