Non-Saturable Passage

The idea that the rodent perinatal BBB is not developed has been extensively revised over the last few decades (Davson and Segal, 1996b). Many of the differences in the BBB of developing and adult animals, w hich w ere ascribed to an immature brain, are now know n to be adaptions to the altered demands of the CNS. For example, some amino acids enter the CNS of neonates more rapidly than the CNS of adults not because the BBB is defective, but because BBB amino acid transporters altered to favor their transport. The BBB is slave to the CNS and so the reason the BBB transports them more avidly is because they are in greater demand by a developing CNS. Most of these adaptations involve transporter mechanisms. In comparison, non-saturable passage is not altered W ith development (Comford et al., 1982). 

The hallmark of non-saturable passage is that the percent of material orossing into the CNS is not affected by the amount of material available for transport. The tw o main mechanisms of non-satiu able passage are transmembrane diffusion and the extracellular pathw ays. The former is much better studied and its principles are wddely applied by industry for the development of CNS drugs the latter has received much less attention. 

Figure 4.1. Tlie vasculai blood-brain barrier tliree levels of complexity. The upper panel illustrates tlie brain endotlielial cell. Tliis is tlie functional and anatomical site of botli banier function and of saturable and non-saturable mechanisms of passage. The major modifications allowing botli banier function and selective penetration of substances ai e indicated. Tlie middle panel illustrates otlier cell types and sti uc-tures important in BBB function. Pericytes are embedded in a basement membrane and asti ocytes foim a net-like structure over tlie capillary bed. Botli cell types are in paracellular communication witli tlie brain endotlielial cells. Pericytes and asti ocytes to some extent oppose each o tilers effects on BBB functions. Tlie lower panel illusti ates tlie neurovasculai unit, a concept, tliat emphasizes inlegration of peripheral, BBB, and centi al inleractions.

Dicblorodifluoromethane (Freon 12) 175-71-8] M 120.9, m -158", b -29.8"/atm, 42.5"/10atm. Passage through saturated aqueous KOH then cone H2SO4, and a tower packed with activated copper on Kielselguhr at 200° removed CO2 and O2. A trap cooled to -29° removed a trace of high boiling material. It is a non-flammable propellant. 

Isolation of the hydrocarbons from other lipids The total lipid extract may be subjected to removal of elemental sulphur by passage through an activated copper column (Blumer, 1957) and then to chromatographic separation on adsorbent columns or thin layer plates. For column chromatography, silic el is used with a short alumina bed on the top of the silic el. Both adsorbents should be partially deactivated by the addition of water (2—5%) to prevent the formation of artifacts (Blumer, 1970). Elution with a non-polar solvent such as hexane or pentane and subsequently with mixtures of non-polar and polar solvents, e.g. benzene and methanol, permits the isolation of several fractions containing saturated, unsaturated, aromatic hydrocarbons and more polar compounds (methyl esters, alcohols, acids, phenols and heterocyclic compounds). The interference from esters encountered in the isolation of aromatic hydrocarbons can be avoided prior to separation by saponification of the esters of fatty acids, which are easily removed. 

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