1. Generalized changes in blood-brain barrier (BBB) permeability are accompanied by extravasation of plasma proteins; thus, they are readily studied with protein markers or protein-dye complexes. Selective changes in permeability involve alterations in BBB transport systems; they are best studied with techniques which detect the qualitative hallmarks of carrier-mediated transport, namely saturation, competition, and stereospecificity. 2. Quantitative assessments of the selective permeability of the BBB can be made from the saturation data expressed in terms of Michaelis-Menten kinetics. The advantages of the latter are twofold: (a) alterations elicited by modified barrier affinity (Km) can be distinguished from alterations in carrier capacity (Vmax); (b) the relative rates of flux of a metabolite across the BBB can be placed in the perspective of cerebral metabolism. Kinetic data on transport processes in the BBB are obtained by either constant infusion or single injection techniques. Results obtained with both methodologies have been comparable. 3. Independent transport systems for glucose, neutral amino acids, basic amino acids, and monocarboxylic acids have been identified in the BBB. The description of these transport systems in kinetic terms provides a background of information on intact mechanisms to which altered transport can be compared. 4. Experimental evidence indicates that the availability of key metabolic substrates, such as glucose or essential amino acids, may be rate-limiting in cerebral metabolism. A working hypothesis was developed that the consequences of a selective change in barrier permeability to one or more of these essential substrates are directly related to altered rates of reaction in substrate-limited pathways, e.g., cerebral protein or neuro-transmitter biosynthesis. 5. Toxicological causes of generalized changes in BBB permeability include hypertonic solutions, organic solvents, surface-active agents, enzymes, and heavy metals. Some agents, e.g., mercury or hypertonic urea, induce selective changes in BBB transport at doses much lower than those required for nonspecific barrier break-down. Subtle changes in transport of metabolic substrates may remain unrecognized unless specifically investigated, yet may have profound consequences on brain metabolism. 6. Pathological processes can also induce selective changes in BBB permeability. Such changes often temporally precede the more generalized alterations in permeability that can occur during pathogenesis. For example, in brain edema due to an ischemic infarct, glucose transport increases during the early cytotoxic phase, whereas generalized changes are not detected until the later vasogenic phase.

—Alterations in the localization and concentration of zinc in the hippocampus and in other regions of rat brain were studied during postnatal maturation. Histochemical observations indicated increasing levels of zinc in the hippocampal mossy fibre layer at about 20 days of age. Between 18 and 22 days, hippocampal levels of zinc increased by 35 per cent to reach adult levels (121 ng/mg of protein). After subcellular fractionation, more than one‐half of the hippocampal zinc was found in the first pellet (P1; 1085 g– 10 min), where large boutons would be expected. Autoradiographic evidence, revealing the sequential location of positron tracks first in the granular cell layer and later in the mossy fibre layer, raises the possibility of axoplasmic transport of zinc from granule cell perikarya to their terminal boutons. Our data suggest that zinc may be involved in the maturation and function of the mossy fibre pathway.

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