CHEMICAL ENVIRONMENT OF THE CENTRAL NERVOUS SYSTEM 



1885 



potential difference between the blood stream and 

 the intracranial extravascular fluids which was 

 uniquely sensitive to [H + ] and [K + ], obeying the 

 following relationship with respect to pH: 



[H + ] a 



^P.D. 



kA log w 



[H + ]i 



where [H + ] a is the hydrogen ion concentration of the 

 arterial blood and [H + ]; is the hydrogen ion concen- 

 tration of the central nervous system interstitial 

 fluid. For the central nervous system-blood potential 

 difference in millivolts between cerebral cortex and 

 jugular blood of rabbits and rats, k was found to be 

 29 =fc 5 mv. These results are interpreted as indicating 

 a source of emf across the panvascular blood-brain 

 barrier which resembles a membrane diffusion poten- 

 tial. The blood-brain barrier is postulated to be more 

 permeable to H + and K + than to anions and other 

 cations, and the presence of this electrical potential 

 is proposed to be related to a secretory process in- 

 volved in regulating the central nervous system en- 

 vironment. 



This electrical evidence for relatively free move- 

 ment of H + across a membrane separating the plasma 

 from the central nervous system extravascular fluids 

 does not require that changes in plasma [H + ] are 

 readily reflected in extravascular fluid [H + ]. On the 

 contrary, analogous to nerve cell membranes where 

 K + permeability is relatively high, but little net 

 movement of this ion occurs, it is suggested that al- 

 though the mobility of H + across the blood-brain 

 barrier is high, net movement of this ion between the 

 intravascular and extravascular compartments is 

 limited by electrostatic forces because of the sharply 

 reduced mobilities of Cl~ and other anions. The 

 relative inability of metabolic acidosis and alkalosis 

 to produce a change in cerebrospinal fluid pH has 

 been described by De Bersaques (28) following intra- 

 venous infusion of HC1 or NaHCOa solutions. Leusen 

 (99, 101) had previously discussed the rapid and 

 marked changes in cerebrospinal fluid pH which 

 accompany respiratory acidosis and alkalosis produced 

 by inhalation of gases with high CO -2 contents, or 

 hyperventilation. As early as 1925, Cestan et al. (21) 

 measured pH of the blood and cerebrospinal fluid 

 during acidosis induced by morphine and chloroform 

 anesthesia, and reported that under these circum- 

 stances the changes in H + concentration of these two 

 fluids paralleled each other. They noted further that 

 experimental acidosis produced by intravenous injec- 

 tion of HC1 did not decrease the pH of the cerebro- 

 spinal fluid, but instead caused it to become slightly 





RABBIT 5/8/55 

 Nembutal anesthesia 

 d - tubocurorine 



0, 



IOOV*« 



-IO*CO,'90%0,- 



Arttciol pH 



INTRAVENOUS INFUSION OF HCL— ► 



2 4 6 3 10 12 14 IS IS 20 



TIME i minutes) 



fig. 7. Representative curves contrasting the lack of elicit 

 on the brain pH of intravenous HO with the depression of brain 

 pH resulting from C0 2 inhalation. The initial blood alkalosis 

 was produced by artificial hyperventilation. [From Tschirgi 

 (147) 



more alkaline. It has also been shown that the move- 

 ment of HCO, from plasma to cerebrospinal fluid 

 must occur at an exceedingly slow rate in view of the 

 slight change in cerebrospinal fluid alkali reserve 

 following intravenous administration of NaHCOa 

 in amounts sufficient to markedly increase the alkali 

 reserve of the plasma (25). Therefore it appears that 

 the decrease in central nervous system pll during 

 COs administration results from the rapid diffusion 

 of molecular COs into the extravascular fluids rather 

 than net movement of H + as such from the plasma. 



These relationships are illustrated in figure 7 

 (163, p. 136) from data obtained by simultaneous 

 continuous measurement of arterial blood pH and the 

 pH of the surface of the cerebral cortex. During 

 respiratory acidosis (increased COs), both the hydro- 

 gen ion concentration in the blood plasma and in the 

 extravascular interstitial and cerebrospinal fluids 

 increase considerably, with the change in the plasma 

 being somewhat greater. However, for a comparable 

 increase in plasma [H + ] during metabolic acidosis 

 (HC1 infusion), little if any change in interstitial and 

 cerebrospinal fluid [H + ] occurs. 



To the extent that this barrier to net transfer of H + 

 from plasma to extravascular fluids is coextensive 

 with the central nervous system vasculature, then to 

 this extent must the functional consequences of 

 directly altering plasma pH not result from an altered 



