1772 



HANDBOOK OF PHYSIOLOGV 



NEUROPHYSIOLOGY III 



the ciliary body to enter the secretory cells of the epi- 

 thelium; these cells are continually ejecting; a fluid — 

 the primary aqueous humor —into the posterior 

 chamber. The greater the ease with which a substance 

 may pass into these cells, the greater will be the con- 

 centration in the secretion and thus the greater the 

 rate at which ii passes into the aqueous humor. Ulti- 

 mately, however, the rate of flow of fluid will provide 

 an upper limit to the rate at which the substance may 

 enter the aqueous humor, unless there is a subsidiary 

 mode of penetration. 



b) Such a route is provided by diffusion of the sub- 

 stance out of the capillaries in the iris and thence, 

 through or between the mass of connective tissue cells, 

 into the fluid in the anterior chamber. Here, again, 

 lipoid solubility probably plays a part since the ability 

 to pass through the iris may depend critically upon the 

 ability of the molecule to pass through — rather than 

 around — the connective tissue cells. 



e) Certain substances, like the plasma proteins and 

 rather large water-soluble molecules, e.g. those of 

 sucrose, inulin and /j-aminohippurate, cannot be ex- 

 pected to pass into cells, and their ability to cross the 

 blood-aqueous barrier must depend on their ability to 

 pass through intercellular spaces, i.e. between the cells 

 of the ciliary epithelium. If the number and size of 

 these leaks are limited, the rate of penetration of the 

 barrier by substances confined to this mechanism may 

 be very small indeed. 



Accordingly, the greater the extent to which a sub- 

 stance may use all these routes into the aqueous hu- 

 mor, the greater will be the rate at which the plasma 

 comes into equilibrium with the aqueous humor when 

 the concentration of this substance in the plasma is 

 altered (or vice versa). Thus alcohol penetrates cell 

 membranes very rapidly and when a high concentra- 

 tion is established in the plasma the concentration in 

 the aqueous humor rises to that in the blood very 

 rapidly i t68); in this case .ill three routes are doubt- 

 less available. Sucrose penetrates the barrier slowly; 

 ii presumably uses only the third route. Urea pene- 

 trates more rapidly than sucrose but much less rapidly 

 than alcohol; there is reason to believe thai its main 

 route "l entr) is in the primary secretion, very little 

 entering by the other um routes 



Blood ' erebrospinal Fluid Barriet 



Ii is nub recent!) thai quantitative studies on the 



blood-cerebrospinal fluid barrier have been made, 



■< K .in .1 resull oi the availability ol isotopes I ;i -33, 



77, iit>, 218 220, 224). A simultaneous study of the 



table 4. Values of k llul Deduced from Curves 

 of Penetration into the Aqueous Humor and 

 Cerebrospinal Fluid of the Rabbit 



[After Davson (58)] 



penetration of a variety of substances in both the 

 aqueous humor and cerebrospinal fluid of the rabbit 

 (j7> 58) gave the values of k shown in table 4. It will 

 be seen that the same general rule applies to both 

 systems, namely that penetration is highly specific and 

 that lipoid solubility is a dominant factor. By applying 

 the same sort of analysis as that employed with the re- 

 sults on the aqueous humor, the process of penetration 

 into the cerebrospinal fluid may be described in terms 

 of similar mechanisms, namely penetration into the 

 primary secretion in the ventricles, penetration 

 directly from blood independently of this secretion 

 (analogous to the direct diffusion across the irisi and 

 finally, leakage through large pores permitting the 

 passage of large water-soluble molecules including the 

 plasma proteins. The question of greatest interest is 

 what is meant by the direct diffusion into the cerebro- 

 spinal fluid. This must occur mainly in the subarach- 

 noid space, and one may ask whether the diffusion 

 occurs direct 1\ from the vessels of the pia or less di- 

 rectly from the capillaries of the nervous tissue and 

 subsequent diffusion from the extracellular fluid of 

 this tissue into the cerebrospinal fluid. To resolve lliis 

 we must know what happens to the substances passing 



from the blood to the nervous tissue. Docs the concen- 

 tration in this tissue keep pace with that in the cere- 

 brospinal fluid, or does it keep ahead, or lag behind? 



II the concentration is ahead, clearrj there will be the 

 possibility of a diffusion from nervous tissue to the 

 cerebrospinal fluid, whereas il the concentration in 

 the tissue lags behind, the latter will gain material 



from the eerebrospin.il fluid. We are therefore con- 

 cerned with the blood-brain-barrier the ease with 

 which substances pass oul of the blood into the central 



