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  • Title: [The blood-brain barrier. II. Physiological data (conclusion)].
    Author: Lefauconnier JM, Hauw JJ.
    Journal: Rev Neurol (Paris); 1984; 140(2):89-109. PubMed ID: 6143382.
    Abstract:
    The first part of this review was concerned with morphological data. The second part dealt with the general mechanisms and methods of study of the transport of low molecular weight substances, and with water and electrolytes transport. In this third part, the transport of hydrophilic and lipophilic substances, drugs and neurotransmitters is reviewed. In addition, the developmental characteristics of the BBB and its regulation are described. Hydrophilic substances cannot penetrate the lipid walls unless they are transported through the membranes by a proteinic carrier process. Thus far 9 carrier transport systems have been described for the brain capillaries: 1 for hexoses, 4 for amino acids, 1 for short chain monocarboxylic acids, 2 for nucleic acid precursors and 1 for choline. The blood-brain transport step may play an important role in metabolic utilization of some of these substrates by the brain. The penetration of lipophilic substances across the BBB is dependent upon the following four factors: 1) lipophilia of their undissociated form, (accounted for in their oil/water coefficient); 2) ionic dissociation at plasma pH (only the undissociated form is able to cross the membrane); 3) binding to plasma proteins; 4) molecular weight. The penetration of drugs into the central nervous system is dependent upon these 4 factors. Several trials have been made to enable the passage of normally excluded substances of pharmacological interest: in situ injection; administration of pro-drugs and of liposomes; osmotic opening of the BBB. The peripheral pool of neurotransmitters seems to be totally excluded from the brain by an enzymatic barrier which catabolizes those which have entered the endothelial cell and thus enhances the barrier effect of the endothelial cell luminal membrane. Developmental modifications in the properties of the BBB are observed. The permeability of the BBB in the young can no longer be considered as unselectively greater than in the adult. Although more permeable to some solutes it is less permeable to others, which perhaps reflects a difference in the metabolic needs of immature and adult brains. The permeability of the choroid plexus falls under peripheral regulation. Such regulation (which might also be central) is suggested for brain capillaries based upon the results of physiologic experiments and the existence on their membranes of receptors to neurotransmitters and of neurotransmitter-stimulated adenylate-cyclase.
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