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HANDBOOK OF l-HYSlOI-OCY 



NEUROPHYSIOLOGY III 



between the interior of cells and the blood plasma was 

 thought to occur through this fluid by passive diffu- 

 sion and convection. In order to prevent the neurons 

 from idly drifting about in this sea of interstitial fluid, 

 the neuroglia were believed to function as a sponge- 

 like skeleton within whose interstices the neurons are 

 caught and the whole central nervous system thus 

 provided with some degree of mechanical rigidity. 

 Although the physiologist seldom allows himself to be 

 restricted by anatomical considerations, the histologi- 

 cal picture obtained by light microscopy did appear 

 to provide evidence for this elegantly simple scheme. 

 Extracellular spaces abounded throughout the sec- 

 tions of central nervous tissue and were dutifully 

 named after their originators as spaces of His, spaces 

 of Held, etc. Elaborate "pseudo-lymphatic" systems 

 wen- desi ribed by which pcrineuronal spaces became 

 continuous with perivascular spaces opening ulti- 

 mately into the subarachnoid space (160, 161). 

 Through these channels cerebrospinal fluid was 

 conjectured to flow, propelled by the pulsations of 

 the blood vessels, perhaps to and fro or perhaps only 

 in one direction. Many authors envisioned these 

 spaces as comprising a microsewage disposal system 

 emptying finally into the subarachnoid cesspool 

 whence the digested residues of neuronal metabolism 

 flowed sluggishly back into the blood stream. Some 

 considered them the rivers of abundance down which 

 streamed, from the cornucopia of the cerebrospinal 

 fluid, all the nutrients and other requirements of the 

 neurons. Still others saw them as highways of com- 

 merce w itli barges ol glm use destined for the furnaces 

 of neuronal metabolism passing garbage scows of 

 refuse headed in the opposite direction. In any case, 

 there appeared to be a continuous and open pathwav 

 between the unique and mysterious cerebrospinal 

 thud and the functional units of the central nervous 

 system, giving rise to the concept that the cerebro- 

 spinal fluid was, indeed, the internal milieu. In the 

 [Q20's, Stern and her collaborators developed a 

 simplified concept which was notable for its graphic 

 imager) and lack of experimental verification (141). 

 I hey conceived ol the cerebrospinal fluid, expressed 

 through the 'barriere hemato-encephalique' into the 

 cerebral ventricles, as percolating centrifugally 

 through the extracellular interstices of the nervous 



tissue like an animated coffee pot, supplying the brain 



with electrolytes en route In 1926 Hauptmann gen- 

 eralized tins functi 65) and declared that the 



cerebrospinal fluid acts as an intermediary between 

 1 ■ 1 . 1 mi and brain for the entire metabolic needs ol 

 that tissue in [93 Spatz introduced a bold antago- 



nistic note by postulating that the penetration of the 

 brain by dyes from the cerebrospinal fluid is strictly 

 a process of passive diffusion without convection and 

 that the brain behaves in this respect like a homogene- 

 ous colloidal mass which contains no free fluid (1:57). 

 Soon thereafter, the concept of the cerelirospin.il fluid 

 as the milieu interne of the central nervous system fell 

 into disrepute and this mystic liquor, which for cen- 

 turies had been thought to contain the highest and 

 most refined essence of life, was relegated to the role 

 of a water bath protecting the submerged brain from 

 external injury. 



The concept of an inward perivascular flow of 

 cerebrospinal fluid was recently revived by Sacks & 

 Culbreth ( 1 3 J ) to explain the penetration into the 

 brain of the radioactive tracer P 3 ' 2 ; and Bricrlev (19), 

 unlike most previous investigators, demonstrated india 

 ink particles in the perivascular spaces of the centred 

 nervous system following their injection into the 

 cisterna magna, from which he implicated the centrip- 

 etal perivascular flow in transmission of infective 

 agents from the cerebrospinal fluid into the brain. It 

 has been suggested by Bakay (9, p. bt ) that Brierley's 

 results with india ink might have been caused b\ an 

 artificial flow in the perivascular system as a conse- 

 quence of the rapid exsanguination used to dispatch 

 the experimental animals. Patek (122) was unable to 

 detect a perivascular circulation of cerebrospinal 

 fluid under normal conditions, in agreement with 

 the older literature ( 134, t6o), but was able to fill the 

 perivascular spaces with india ink and colloidal 

 mercury sulfide, administered imrathccalK , by simul- 

 taneously dehydrating the brain with intravenous 

 hypertonic sodium chloride No perivascular accumu- 

 lation of intrathecal colloidal material occurred in 

 the absence ol such dehv dralion. Recent studies bv 

 Bertrand (15) on the diffusion and absorption within 

 the brain of intracercbrallv administered prussian 

 blue and india ink led that author to emu hide that 

 the transit ol material along perivascular spaces is 

 of minor importance Hak.iv (9) agrees with this 

 conclusion and considers that there is no reason to 

 believe that an intrathecal isotope follows any par- 

 ticular pathway of absorption into the brain. 



Functional Ann/mm oj Fluid Compartments 



But the intercellular spaces remained, and the 

 physiologist filled them with a solution derived from 

 the plasm. 1 bv ultrafiltration which, if not cerebro- 

 spinal fluid, was of similar composition. Since no 

 technique was available to obtain and analyze inter- 





