CHEMICAL ENVIRONMENT OF THE CENTRAL NERVOUS SYSTEM 



I8 77 



The role of the meningeal tissues in the hemato- 

 encephalic barrier has been studied by Rodriguez- 

 Peralta (128), using aminoacridine dyes. Intravenous 

 injections of these compounds result in staining of 

 the dural blood vessels and dural tissue including the 

 mesothelial cells lining the inner dural surface, but 

 they do not penetrate into the arachnoidal tissues or 

 cerebrospinal fluid. This shows, according to this 

 author, that the dural blood vessels share the perme- 

 ability characteristics of all blood vessels outside the 

 central nervous system, and that there is a dural 

 barrier located in that part of the membrane of the 

 mesothelial lining cells facing the subdural space. 

 Absence of staining of the endothelium of the pial 

 blood vessels indicates that there is a pial barrier, 

 similar to this author's previous description of the 

 blood-brain barrier (see above), located in that 

 part of the membrane of the pial vascular endothelium 

 facing the lumen of the vessel. All of these membranes 

 appear to be one-way barriers, since subarachnoidal 

 injections of aminoacridines slain all the meningeal 

 tissues and the walls of their blood vessels. 



In the face of this multiplicity of data <mcl opinion, 

 where is the blood-brain barrier? Unfortunately, 

 radiotracer studies have not provided a direct answei 

 to the question of anatomical locus for the retarded 

 penetration of inorganic ions into the central nervous 

 system, although Bakay (9) has shown with micro- 

 scopic radioautographs that the walls of the larger 

 arteries of the brain concentrate large amounts of 

 P 88 . This technique unfortunately does not provide 

 sufficient resolution to answer the Important question 

 concerning penetration of capillary endothelium. 



What is the milieu of the central neurons? Is it an 

 aqueous, protein-free solution of inorganic elcctroh tes, 

 gases and metabolites? Is it the adjacent membrane 

 of glia cells and fibers? Is it a proteinaceous "ground 

 substance' of complex structure and obscure chemical 

 reactivity? These questions have, as yet, no final 

 answer. 



DYNAMICS OF THE CHEMICAL MICROENVTRONMENT 



I-'.h 1 trolyte Exchange 



The exchange of solvent and solutes between the 

 vascular and extravascular compartments of the 

 central nervous system has received renewed attention 

 since the availability of radioactive isotopes has 

 enabled physiologically important substances to be 

 labeled and traced. Among the early studies devoted 

 to this problem, the classic paper of Greenberg et al. 



(58) demonstrated incontrovertibly that the rate of 

 equilibration of a variety of inorganic ions, both 

 negatively and positively charged, with the extra- 

 vascular fluids of the central nervous system after 

 intravenous administration was uniquely slower than 

 their rate of equilibration with most other tissues. 

 These authors arranged labeled ions in the following 

 order of rapidity of entrance into the cerebrospinal 

 fluid: potassium, sodium, bromide, rubidium, stron- 

 tium, phosphate, iodide. They interpreted these 

 variations in rate of equilibration as signifying selec- 

 tivity of the barrier for different solutes. 



Early observations of marked and prolonged de- 

 hydration of the central nervous system following 

 intravenous hypertonic salt solutions a reaction not 

 occurring in other tissues was presumptive evidence 

 that the central nervous system was penetrated only 

 with difficulty l>\ these ions. Schaltenbrand & Bailey 

 (134) perfused hypertonic sodium chloride solution 

 (10 per cent) through one carotid artery of a dog and 

 distilled water at equal pressure through the other. 

 I In- hydrodynamics of the cerebral circulation are 

 such that the two perfusates remained essentially un- 

 mixed, and consequently one half of the brain was 

 perfused with a hypertonic solution and the other 

 half with a hypotonic solution. The animal shortly 

 succumbed, with convulsions limited to the vide of 

 the bodv opposite the hemisphere receiving the hyper- 

 tonic saline. Gross examination of the brain revealed 

 the side perfused w ith hv perionie saline to be shrunken 

 and dehydrated, whereas the vide receiving the hypo- 

 tonic solution was swollen and edematous. Micro- 

 scopic examination of the side receiving the hyper- 

 tonic saline revealed large, distended perivascular 

 (Virchow-Robin) spaces separating the vessel walls 

 from the i;hal membrane, and on the parenchymal 

 side of this membrane, the intercellular sp.ices were 

 described as markedly reduced, and in many areas 

 almost obliterated, so that the cells were packed 

 tightly together. On the side perfused with hypotonic 

 solution there were no perivascular spaces and the 

 intercellular spaces were greatly enlarged. The 

 authors conclude that the perivascular glial mem- 

 brane is relatively impermeable to sodium chloride. 

 It should be added, parenthetically, that this inter- 

 pretation also requires the vascular endothelium to 

 be relatively permeable to sodium chloride, thus 

 tending to localize this aspect of the blood-brain 

 barrier in the perivascular glia. Bakay (q) dismisses 

 this studv with the statement, "I do not believe that 

 one can come to a definite conclusion from an experi- 

 ment of such short duration," and describes his own 



