1 888 



HANDBOOK or PHYSIOLOGY 



Nil koI'IIYSIOLOGY 111 



of sodium. In the kidney, however, the 'pump' is 

 oriented to nunc X.i' and H_>0 from the extravas- 

 cular fluid (glomerular filtrate) into the plasma, 

 whereas in the brain it is proposed to move these 

 substances from plasma into extravascular fluid. 

 Interference by acetazoleamide with this kidney 

 tubular mechanism in a manner entirely analogous 

 to that proposed for intracranial fluid formation is 

 thought to be responsible for the lack of water reab- 

 sorption and consequent diuresis produced by this 

 compound (14). Since tubular secretion of K. + in 

 exchange for Na + can occur in the kidne\ , and since 

 k * and H' behave similarly with respect to the trans- 

 blood-brain barrier electrical potential difference 

 (see above), the possibility of K + for Na + exchange 

 across the blood-brain barrier must be considered. 



A further consequence of this hypothesis is the pre- 

 diction that acetazoleamide should decrease the rate 

 of accumulation of parenterally administered radio- 

 active sodium in the central nervous system. That this 

 is indeed the case has been shown by Woodbury 

 el til. (168). However, these authors interpret the 

 reduced uptake of radio sodium (Na--) by the brain 

 following treatment with acetazoleamide as resulting 

 not from a decrease in blood-brain barrier transport, 

 but rather from decreasing the influx of sodium into 

 brain cells. They assume originally that the brain 

 chloride is extracellular and present in about the 

 same concentration as in plasma, and thus use the 

 chloride space as a measure of extracellular fluid 

 space of brain. They further assume that the concen- 

 tration of extracellular brain sodium is the same as 

 plasma, and on these two assumptions calculate the 

 ratio of brain extracellular to intracellular sodium. 



On this basis, these authors state that acetazoleamide 

 markedly decreases intracellular sodium concentra- 

 tion in brain tissue (166). Therefore, the reduced 

 turnover of radiosodium in the brain following 

 acetazoleamide is believed by them to indicate a 

 decreased influx of sodium into the cells and a conse- 

 quent decrease in intracellular sodium concentration. 

 This decrease in sodium concentration in cells is sug- 

 gested by these authors as the basis for the general 

 anticonvulsant action not only of acetazoleamide, 

 but also of diphenylhydantoin. Since diphenylhydan- 

 toin, unlike acetazoleamide, increases the turnover 

 of radiosodium between plasma and brain while 

 simultaneously decreasing intracellular sodium con- 

 centration (using; the assumptions mentioned previ- 

 ously), it is proposed that diphenylhydantoin en- 

 hances the active extrusion of sodium from brain 

 cells, thereby lowering intracellular brain sodium 

 concentration. 



Thus Woodbury (167) de-emphasizes the role of a 

 Structural blood-brain barrier separating plasma 

 from central nervous system interstitial fluid and 

 proposes that "the so-called blood-brain barrier is 

 related more to the small volume in which substances 

 distribute rather than to an active extrusion process" 

 (see fig. 1 ). He apparently considers the environment 

 of the neurons to consist of an aqueous milieu the 

 composition of which is determined by ultrafiltration 

 from the plasma, and by active movement of solutes 

 between the interstitial and intracellular compart- 

 ment. 



How main things are left in an uncertain stale 

 for the future ! 



K I I' I. k I'. N CKS 



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■95°- 



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