77 8 



HANDHIHlK 111- I'HYSIOLOGY 



NEUROI'MYSIOLOOY III 



system ol the cerebral and spinal circulations; once it 

 arrives here— in the pericapillary space — its fate will 

 lie determined l>\ the ease with which it may pass the 

 brain-blood barrier (the blood-brain harrier in re- 

 verse). If it is lipoid soluble, it will pass rapidly into 

 the circulation and disappear from the nervous tissue. 

 If it is a water-soluble substance of large molecular 

 weight, like sucrose, ^-aminohippurate or phenol- 

 sulphonephthalein, it will escape only very slowly into 

 the blood stream by this route;- moreover, its rate of 

 loss from the subarachnoid space into the nervous 

 tissue will be low because it will have difficulty in sur- 

 mounting 'he cerebrospinal fluid-brain barrier. Con- 

 sequently, if a series of substances is studied, for ex- 

 ample serum albumin, inulin, sucrose, />-aminohip- 

 purate, creatinine, thiourea, methyl thiourea, ethyl 

 thiourea and ethyl alcohol, we may expect the rates 

 of disappearance to increase in this order. The very 

 large molecular-weight substances, such as albumin 

 and inulin, will escape probably exclusively by the 

 arachnoid villi; the smaller sucrose, /i-aminohippurate 

 and creatinine molecules will escape mainly by the 

 arachnoid villi, but some will leave through the pia- 

 glia to the nervous tissue where it is held up by the 

 brain-blood barrier. With the more lipoid-soluble 

 thiourea, ethyl thiourea and ethyl alcohol, the escape 

 into the nervous tissue becomes the more important. 

 In general, these predictions are confirmed by experi- 

 ment (56, 57, 218). The behavior of P 3 ' 2 -labcled inor- 

 ganic phosphate is of special interest since it is in- 

 volved in the metabolism of the nervous tissue, being 

 rapidly incorporated into organic phosphates (141). 

 When the labeled phosphate is injected into the blood 

 Stream, the uptake of phosphate by the nervous tissue 

 is slow, a fact indicating that the blood-brain barrier 

 to inorganic phosphate is high; when injected into the 

 subarachnoid space, the uptake by the nervous tissue 

 is very rapid (14) so that we may conclude that the 

 passage of this ion across the pia-glia is easy by com- 

 parison with passage across the blood-brain barrier. 21 



20 In tin- spe< ialized regions like tin' area postrema, where 

 the blood-brain barrier is low or absent, we slnml<l expect these 

 large molecular weight and lipoid-insoluble molecules in 

 escape Actually this has been found, although tin- phenome- 

 non seems in have puzzled those who discovered it. Thus 

 Win, II. ml '.■,,' and Mandelstamm & Krylow ii-,ii noticed 

 that these areas did not stain when trypan blue w as injected 

 min the subarachnoid space, although the rest ol tin- brain was 



strong!) -1 1 ll« blood-brain barrier being absent in these 



ins any trypan blue ilillnsmy into them must In- carried 

 ,u\.i\ rapidl) mi" the blood stream An essentiall) similai 

 phenomenon has been noted more recently mi, 12) with 

 1 adioai 11 vi pho iphate 



"These experiments with phosphate are essentially repeti- 

 tions, in -i mori modern fashion, "i the original Goldroann 1 1 <► i, 



Particulate matter, such as carbon particles, thoro- 

 trast, pantopaque, etc., would appear to be largely 

 confined to the subarachnoid space after an intralum- 

 bar or intracisternal injection (92, 215, 233). In 

 chronic experiments there is certainly some escape into 

 the epidural tissue and along the sheaths of the spinal 

 nerves [see, for example, Bricrlcy (40)], but there is 

 little doubt that such escape routes are insignificant 

 as far as the fate of nonparticulate matter is con- 

 cerned. The interpretation of the results of the injec- 

 tion of particulate matter is obscured, moreover, by 

 the inflammatory reaction in the meninges (3, 81, 180, 

 257) and an associated communicating hydrocephalus 

 (183, 204, 234).'-'- 



SPECIAL FEATURES OF CHEMICAL COMPOSITION OF 

 INTRACRANIAL AND INTRAOCULAR FLUIDS 



The main outlines of the chemical composition of 

 the fluids have been sketched earlier; by virtue of their 

 chemical make-up, which differs from that of a dialy- 

 sate of plasma in many respects, the fluids have been 

 described as secretions; that is, taking either fluid as a 

 whole, we may say that special active-transport mech- 

 anisms must have been operative during the process 

 of their elaboration. This does not mean, of course, 

 that every type of molecule or ion entering the fluid 

 from the blood is subjected to special secretory activ- 

 ity; in fact there is good reason to believe that with 

 many substances, in particular the relatively lipoid- 

 soluble materials studied experimentally, simple diffu- 

 sion processes are adequate to account for their 



104) experiments: trypan blue did not pass from blood to 

 nervous tissue, but when injected into the subarachnoid space 

 the tissue was rapidly stained. Tschirgi (223) has shown that 

 the interpretation ol ( .oUlm. inn's experiments is by no means 

 unequivocal, however, owing to the binding of trypan blue to 

 tin- plasma proteins, so that it is unfair to compare the passage 

 of trypan blue from blood (where it is bound to tin- proteins 

 to nervous iisMir, and from the cerebrospinal fluid (where it is 

 free 1 to tin nervous tissue l.xperiments with l >I2 -labelled 

 inorganic phosphate I 1 ; and with \a'-"' (57, 58, 2t8, 224) indi- 

 cate quite unequivocally, however, that passage across tin 

 In .1111-1 erebrospin.il lluid barrier is less restricted than across 

 the blood-brain barrier, this becomes especially apparent when 

 we COnsidei how much more favorable for diffusion are condi- 

 tions in the capillar) bed than in the subarachnoid space I he 

 area of tin capillary bed of the nervous tissue is main times 



greater than that "l tin surface ol the central nervous system. 



Iln I. in u! ih. constituents nl tin blood, plasma proteins 

 and erythrocytes has been investigated b) Courtice & Sim- 

 in.. ii.K ,1 ami Simmonds (208, 209) Red cells an- ver) 

 deftnitel) eliminated limn the subarachnoid space without a 

 preliminary hemolysis; in this respect the) stand out in marked 



1 1.1 u 1 ast to inanimate particulate matter of comparable Size. 



