'774 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY III 



barrier between brain and nervous tissue is either re- 

 duced or nonexistent; these are the posterior lobe of 

 the hypophysis (203), the area postrema in the roof of 

 the fourth ventricle (251 I, (lie pineal body (148), the 

 paraphysis (1 79), the wall of the optic recess (29) and 

 the eminentia saccularis of the hypophyseal stem 

 (250). When trypan blue is injected into the blood, it 

 docs not normally stain the nervous tissue (103); but 

 in these special regions, which are essentially non- 

 nervous regions of the central nervous system, the dye 

 leaves the vascular system and is taken up in visible 

 amounts. Subsequent work in which P :i '--labeled inor- 

 ganic phosphate (11, 12, 185) and bromide (117) 

 were employed has confirmed that these regions are 

 regions of increased permeability of the blood-brain 

 barrier. Whether the low blood-brain barrier in these 

 regions has any special physiological significance so 

 far as function of the brain as a whole is concerned, or 

 whether it is an accident following from the circum- 

 stance that the tissue in these regions is essentially 

 nonneural, is a matter that cannot vet be decided. 



Penetration into Different Regions 

 of Cerebrospinal System 



We have so far treated the cerebrospinal fluid as a 

 whole. When ii is appreciated that this fluid not only 

 occurs in the ventricles but is spread over the whole 

 surface of the central nervous system, it will not be 

 surprising to find that when a substance is injected 

 into the blood, it will find its way into some regions 

 more rapidly than into others. Thus, if our present 

 \ iru point is correct, the most important site of pene- 

 tration is in the ventricles. It is here that the fluid is 

 primarily secreted so that if a substance penetrated 

 from blood to fluid predominantly in this priman se- 

 cretion, and only secondarily by direel diffusion into 

 the subarachnoid fluid, we should expect to find a 

 very marked degree of inhomogeneity in the fluid 

 during the approach to equilibrium. Studies on man 

 have, indeed, shown that all parts of the cerebrospinal 

 System do not come into equilibrium with the blood 



at the same rate. Intravenous X.r-' 1 , lor example, 

 come- into equilibrium more rapidly with the ven- 

 tricles than the cisternal or lumbar fluids (219, 220, 

 j j 1 1 Water, alcohi >l .mil ethyl thiourea are very rapid 

 penetrators "I die barriers. This means thai the direel 

 penetration into the subarachnoid fluid hum be very 

 in. mi, mi that we mighl expect .1 mini- uniform 

 approach to equilibrium. Actually the subarachnoid 

 fluid cuiiics into equilibrium more rapidly than the 

 ventrii ular, so far .is water and alcohol are concerned 



(31, 219); with ethyl thiourea, the equilibration is al- 

 most uniform (57, 58). " 



Breakdown of Barriers 



The aqueous humor and the cerebrospinal fluid 

 normally contain small concentrations of the albumin 

 and globulin fractions of the plasma proteins. 1 - Analy- 

 sis of the fluids in the anterior and posterior chambers 

 (205) has shown that the posterior chamber fluid con- 

 tains proteins in about the same concentration as in 

 the anterior chamber so that we may assume that 

 during the elaboration of the primary fluid appre- 

 ciable amounts pass from the ciliary processes — pre- 

 sumably between the epithelial cells — to mix with the 

 fluid elaborated by the cells. A similar state of affairs 

 probably exists in the ventricles. That the fluids are 

 constantly being drained away must mean that the 

 wall of Schlemm's canal and the mesothelial lining of 

 the arachnoid villus are permeable to these large 

 molecules; if they were not, they would be retained 

 and the concentration of proteins would build up to 

 values comparable with those in the plasma. The 

 globulin molecule is considerably larger than that of 

 the albumin, however, and it may be that the gener- 

 ally higher values for the albumin globulin ratios 

 found for the fluids reflect the tendency for the sjlobu- 

 Iin molecules to be filtered back to a small extent in the 

 drainage channels. 11 



When aqueous humor is withdrawn from the an- 

 terior chamber, the latter rapidly refills so that within 



u Eichler & binder 177) examined the penetration of Na 2 ' 

 from the blood into different regions of the spinal subarachnoid; 

 according to them, the lumbar region was the most favored 

 and they argued that there was a lumbar source of secretion of 

 the Quid. Their results with injections directly into the spinal 

 arachnoid certainly suggested a cranially directed How. Becker 

 j (. -v disputes the conclusions of Eichler & Lander. "See also 

 Eichler it at. (78). 



"The various fractions of the proteins in the fluids have 

 hem analyzed by electrophoretic methods, they would appear 



to correspond with those in the plasma although the albumin 

 globulin ratio is usually higher in the Quid. See von Sallmann 

 & Moore (227), Witmei 252 Niedermeyei 165 . Munich 

 164) and I svii ■■ . 80) foi tin aqueous humor; and Kabat 

 el at. (129), Scheid & Scheid 197, 198), Essei & Heinzlei 9 

 and Rossi & Schneidei 192 , among many others, fur the 

 1 1 1 ebrospinal fluid. 



11 It may also be due to the more rapid penetration of the 

 albumin molecules into tin- fluid. Hie problem as to the 

 limiting size "l tin- pai tit les thai ma; leave the anterior cham- 

 ber has been examined experimental!) I>\ Hugger) and Ins 

 co-workers (124, i. ,r , . and In 1 00 



