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• W96677421 abstract "The blood-brain barrier prevents an indifferent medicine existing in the blood to enter also in the brain. This barrier has got an anatomical base: it is first consisting in a cerebrovascular layer of endothelial capillary vessels of the peripheral tissue. It is moreover covered by outgrowths of the flial cells, which are called astrocytes. There are, for that reason, important limits to a size of molecules which can reach the cerebral tissue through a paracellular way (through what is called in English tight-junctions). Most medicines must use the transcellular way. Lipophily is necessary to follow that way. Year after year, it appeared, thanks to a comparative study of the substances, that there exists--grosso modo--a positive correlation between the lipophilic level and the permeation-level of a substance in the cerebral tissue. There are, however, several exceptions: it is so that hydrophilic substances, possessing an important nourishing function (such as glucosis, amino-acids) seem to penetrate much more easily than we could expect when we consider their physicochemical characteristics. This is the result of the fact that there exist specifical transport-mechanisms for these substances at the level of the endothelial cell-membranes, allowing the penetration of such substances. There exist, on the contrary, lipophilic components that penetrate the cerebral tissue much less strongly than we should expect. This happens because there also exist pumping-mechanisms at the level of the hemato-encephalic barrier. The concerning substance, which was recently discovered is the glycoprotein P, which is also responsible for the multi-drug-resistance and for the resistance of tumors to cytostatics. This phenomenon relies on a very efficient pumping of substances which have penetrated cells in which this protein expressed itself in the membranous structure. In order to obtain a better understanding of the function of the hemato-encephalic barrier, comprising the transport of medicines, it is most important to have reliable experimental models. It is to that aim that, during former years, the technique of cultivating endothelial cerebrovascular cells was developed. These cells are isolated from brains of calves or rats and, subsequently, cultivated on a laboratory medium; about a week later, they have grown a single and confluent layer. This layer represents a kint of hemato-encephalic barrier in vitro, which allows us to study the transfer of substances through the layer and thus also the details concerning the transport mechanisms, as well as the factors influencing the permeability of the cells-layer (for instance the inflammatory stimuli). Concerning the in vivo research, the technique of intracerebral microdialysis in lab-animals proved to be very promising. In order to effect this microdialysis, a semipermeable microcannula is introduced in the brain tissue, across which an iso-osmotic liquid is being injected continuously. The substances staying in the interstitial liquid of the cerebral tissue will diffuse under the influence of a concentration gradient, into the dialysing liquid and they will also be ready to be analysed. Thanks to this technique, it is possible to follow, in the same animal, the evolution of the concentration in the brain of a substance which has, for instance been injected in a peripheral region. In this way, we obtain, indirectly and in vivo, informations about the functioning-process of the hemato-encephalic barrier. We can, moreover, effect measures on a specific spot, for instance in tumoral brain tissue: this allows us to study the influence of specific transport-mechanisms. These rather recent techniques, as well in vitro as in vivo, will allow us, in consequence, to increase, during the next years, our understanding of the way the hemato-encephalic barrier functions as to the transfer of medicines towards the central nervous system. This understanding may lead us to new strategies allowing" @default.
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• W96677421 date "1991-01-01" @default.
• W96677421 modified "2023-09-27" @default.
• W96677421 title "Transport of Drugs Across the Blood-Brain Barrier: In Vitro and in Vivo Strategies" @default.
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• W96677421 doi "https://doi.org/10.1007/978-1-4757-0286-6_14" @default.
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