Blood-brain barrier, concepts

Basic Concepts Underlying the Pharmacogenomics of the Blood-Brain Barrier... 

Basic Concepts Underlying the Pharmacogenomics of the Blood-Brain Barrier 317 15.1.2.3 Astrocytes in the Blood-Brain Barrier... 

Bradbury, M., The Concept of a Blood-Brain Barrier. John Wiley, Chichester, 1979. Caroscio, J. T., Kochwa, S., Sacks, H., Cohen, J. A., and Yahr, M. D., Quantitative CSF IgG measurements in multiple sclerosis and other nerrrologic diseases. Arch. Neurol. 40, 409-413 (1983). 

F2. Felgenhauer, K., The filtration concept of the blood-CSF barrier as basis for the differentiation of CSF proteins. In New Concepts of Blood-Brain Barrier (L. Greenwood, D. J. Begley, M. B. Segal, and S. Lightman, eds.), pp. 209-217. Rlenum Rress, London, 1995. 

Engelmann M, Landgraf R, Wotjak CT (2004) Interaction between the hypothalamic-neurohypophysial system (HNS) and the hypothalamic-pituitary-adrenal (HPA) axis under stress—an old concept revisited. Front Neiu oendocrinol 25 132-149 Ermisch A, Riihle HJ, Landgraf R, Hefi J (1985) Blood-brain barrier and peptides. J Cereb Blood Flow Metab 5 350-357... 

The partition coefficient and concepts derived from it are particularly important in explaining the mode of action of neurological drugs, such as anticonvulsants (chapter 8, section 8.1.5) and general anesthetics, which must penetrate the blood-brain barrier prior to exerting their biological effect. 

Bradbury, M. (1979) The Concept of a Blood-Brain Barrier, Wiley, Chichester, New York... 

In order to improve cell and blood-brain-barrier permeability of the polar tetrahydropterins model studies were performed by applying the concepts of the Bodor system. 6-Mono- and 6,7-disubstituted 5,6,7,8-tetrahydropterins (172) have been acylated with nicotinoyl chloride at N-5 (173) followed by quaternization of the pyridine moiety by various alkyl and aralkyl halides (174), respectively (Scheme 27). Reduction of the pyridinium residue to its 1,4-dihydro stage afforded new types of potentially active conjugates (175) (Scheme 27) <90MI 718-07,91MI718-03). 

Bradbury M. The concept of a blood-brain barrier. New York John Wiley, 1979. p. 465. 

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.

Greenwood J, Bamforth S, Wang Y, Devine L (1995) The blood-retinal barrier in immune- mediated diseases of the retina. In New Concepts of a Blood-Brain Barrier (Greenwood J, Begley DJ, Segal MB, eds), pp 315-326. New York Plenum Press. 

In particular, the proposed gliovascular units, in which individual astrocytic glia support the function of particular neuronal populations and territories, communicate with associated segments of the microvasculature [43, 44]. This novel concept of single functional units over the total BBB structure is in concordance with Ge et al. [45], who summarized many data supporting differences in the expression levels of several BBB markers in arterioles, capillaries, and venules and asked finally where is the blood-brain barrier. .. really ... 

The concept of using carbamates as pretreatment which protects against OP intoxication was first mooted in 1956 by Koster who demonstrated that cats pretreated with a small dose of eserine (physostigmine) survived poisoning by supralethal doses of diisopropylphosphorofluori-date (DFP) (Koster, 1956). Subsequently, Berry and Davies (1970) demonstrated the effectiveness of a combination of atropine and carbamate pretreatment against soman poisoning. At that time, it was not considered that pretreatments with substances such as atropine, with marked actions on the central nervous system, would be acceptable for human use. For this reason, effort was concentrated upon pretreatment with pyridostigmine, a quaternary carbamate, which would not be expected to cross the blood-brain barrier and affect the central nervous system. 

Finally, prodrugs were first synthesized before the concept was introduced by Albert. As an example, heroin is to some extent an "accidental" prodrug. As a matter of fact, morphine crosses the blood-brain barrier relatively slowly. Diacetylmorphine (heroin) has a greater lipid solubility, and thus transfers into the brain, where hydrolysis converts heroin to morphine. The latter is ultimately responsible for the pharmacological effect (10). This is a good example of a prodrug that has found unintended use outside the field of medicine,.although it has also been used to treat chronic pain. 

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