The types of mechanisms present at the blood–brain barrier that allow easy passage of nutrients like glucose and amino acids and wastes like CO2 are shown in Fig. 3 along with indication of the need for expulsion of substances that should not be allowed to enter or accumulate in the brain. Because the gaps between the endothelial cells are occluded by tight junctions that greatly reduce the paracellular passage of solutes even as small as sugars and inorganic ions like Na+, K+ and Cl−,4 to enter or leave the brain across the blood–brain barrier almost all substances must pass through the cells, which means they must cross both the luminal and abluminal membranes.
Fig. 3 Mechanisms for transfers into and out of the brain across the blood–brain barrier and the need for efflux mechanisms. Passive, non-specific transfers can occur via paracellular and transcellular routes, though the rates for paracellular transfer are small. Specific transcellular transport can be passive or active. In addition to the transfers for well-known substances many others are able to enter at various rates, either because they are sufficiently small and lipid-soluble or because barrier mechanisms are not perfect. Substances which enter even though they shouldn’t or are produced “accidentally” by metabolism cannot be allowed to accumulate within the brain. Thus there must be mechanisms for eliminating them