1 868 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY III 



ment and the cerebrospinal fluid are postulated to 

 exchange with the rapid phase of the interstitial 

 compartment. These relationships are summarized 

 in figure i (167, fig. 38) which attributes the slow 

 phase of the interstitial compartment to the glia, 

 which the author apparently considers to be extra- 

 cellular. However, electronmicrographic studies (see 

 below) do not support this concept of an extra- 

 cellular 'glue' occupying over 20 per cent of the brain 

 volume, and if, indeed, the slow phase does represent 

 penetration into neuroglia, it must be considered 

 as part of cell permeability. It is interesting to note 

 thai the volume of the 'true' morphologic extra- 

 cellular space of rat cortex has been estimated from 

 clectronmicrographs as approximately 4 per cent. 



For the electrophysiologist, the existence of an 

 extracellular continuous phase of conducting fluid 

 surrounding the membranes of cellular elements has 

 been the foundation of his theoretical interpretations. 

 As his microclcctrode descends, micron by micron 

 through cortical tissue, he visualizes the tip passing 

 into a lacuna of interstitial fluid through which cur- 

 rents generated by adjacent neurons are flowing. 

 As the height and form of the oscilloscope tracing 

 change, he envisions the electrode approaching a cell 

 membrane and then, with an electrical snap, pene- 

 trating to the interior. Thus, the electrical resistance 



CSF 



1 



PLASMA: 



90Min. 



13 Min. 



:± RAPID PHASE — 

 4% 

 1 

 24 Hrs. 



SLOW PHASE 



(GLIA) 



21% 



l3Min 



: CELLS 



54% 



Wet -Dry wt meosures total HgO 



CI space meosures total E.C.W. 



Total HgO-totol E.C.W. measures cell HjO 



S s5 4 space measures ropid phase of E.C.W 



Total E.C.W -Ropid Phose measures slow phase of E.C.W. 



hi; ! Woodbury's r 1 uh'i' 1 it ul tin' \.iriuii.s lluid compartments 

 in the cerebral cortex. Time Indicated on the arrows is the hall 



1 I"! equilibration of a solute across that particular phase 



boundary. The figure under each phase is the percentage ol 

 total water in that phase I ( 11 , extracellular water; 'V 

 cerebrospinal fluid A possible route oi transfei ol materials 

 from plasma directly to cerebrospinal fluid is not indicated 

 on tbis diagi am From w oodbui j 



of central nervous tissue has also been interpreted to 

 require a sizeable volume of interstitial fluid in the 

 belief that "the brain consists of cells and fibers sur- 

 rounded by relatively high resistance membranes, 

 which are embedded in an intercellular mass of rela- 

 tively high specific conductivity" '151). 



Attempts to utilize foreign substances, which 

 equilibrate rapidly between blood and interstitial 

 fluid but do not penetrate rclls, have been relatively 

 unsuccessful for estimating central nervous system 

 extracellular space. Inulin, with its high molecular 

 weight, lipoid insolubility, low osmotic activity in 

 readily detectable concentrations and lack of toxicity, 

 has been widely used for determining total body extra- 

 cellular space or, by use of tissue samples, for specific 

 organs. Other substances which have compared favor- 

 ably with inulin include ferrocyanide, radioactive 

 sulfate and thiosulfate. When administered in vivo, 

 however, these substances are effectively blocked 

 from entry into the brain and cerebrospinal fluid l>\ 

 the blood-brain barrier, and are therefore unsuitable 

 for determining the extracellular volume of the 

 intact central nervous system. In an effort to sur- 

 mount these difficulties, Allen (3) utilized an in vitro 

 diffusion technique with slices of rat brain incubated 

 in appropriate media containing inulin or ferro- 

 cyanide which had been shown by Weed (160) not 

 to penetrate the living cells of nerve tissue. After 

 determining the amount of tissue swelling which 

 had occurred, the ferrocyanide (or inulin 1 space was 

 calculated as ml per 100 gm of tissue by the follow inn 

 formula : 



ferrocyanide space (ml 100 gm) 



ferrocyanide in tissue ( mc; uni 

 ferrocyanide in medium (mg ml) 



X 100 



Following an initial period of rapid diffusion of 

 the ferrocyanide or inulin into the tissue slice, .1 

 slower and linear increase in volume of the space 

 continued for a hr., due most likeiv to the gradual 

 penetration of the material into the cells. Extrapola- 

 tion of this phase of the curve to zero time indicated 

 ,m extracellular space for rat cerebrum of 1 7 per cenl 

 using ferrocyanide and 14.5 per cent using inulin. 

 Determination of chloride space in similar tissue 

 slices ,u zero time, assuming equilibration with 

 cerebrospinal fluid chloride, averaged ji per cenl, 

 which is comparable n> that reported by others and 

 almost twice as large .is the inulin-ferrocyanide 

 space. 



[f the lissur ih hd ol 1 .it brain is assumed to be identi- 



