CHEMICAL ENVIRONMENT OF THE CENTRAL NERVOUS SYSTEM 



'879 



tion gradually gives way to a comatose state which not 

 many animals survive. Stronger solutions cause a 

 more stormy scene, but of shorter duration; the animal 

 succumbs in 1 5 to 20 minutes. When 3 minims of a 

 1 % solution are injected the animal runs about in- 

 cessantly for an hour and longer and then falls into a 

 paretic state lasting for hours; but the animal re- 

 covers." 



Meltzer also demonstrated the opposite effect of 

 intracerebral injection of magnesium sulfate, follow- 

 ing which the rabbit became paralyzed in a short 

 time without preceding convulsions. 



The studies of Stern & Chvoles (140), Resnik et al. 

 (125), Mullins et al. (117), Stern (138, 139), Down- 

 man & Mackenzie (31), von Euler (154), Walker 

 (156), Leusen (100, 101), Koenigstern (96), and 

 Horsten & Klopper (83) provide a full survey of the 

 effects of intracisternal and intraventricular injections 

 of K + salts and of modifications in the electrolyte 

 balance produced in other ways in the cerebrospinal 

 fluid in the region of the medulla oblongata. In gen- 

 eral, when a solution with .111 abnormally high K' 

 Ca ++ ratio (due cither to excess K + or deficient 

 Ca ++ ) is injected intracisternally, there is initially 

 increased muscular activity and stimulation of respira- 

 tion, followed by a rise of arterial pressure and cardiac 

 slowing. Small doses of K.C1 usually produce an initial 

 fall of arterial pressure (from 50 to 120 mm Hg) 

 associated with bradycardia. With sufficiently large 

 doses of KC1, respiratory stimulation is replaced by 

 apneusis, associated with circulatory collapse. These 

 effects are generally attributed to an action, first 

 stimulant and then depressant, on the various medul- 

 lary centers, vasoconstrictor, vasodilator, cardio- 

 inhibitory, cardioaccelerator, respiratory, etc. 



Stern & Chvoles (140) found that the introduction 

 of potassium into the cerebral ventricles of dogs and 

 cats caused an elevation of the arterial pressure, and 

 a stimulation of the pressor and an inhibition of the 

 depressor reaction of the carotid sinus reflexes. The) 

 noted, on the other hand, that calcium had a reverse 

 effect, and that injection of equivalent amounts of 

 Ca" 1-4 " and K + had no effect. They concluded that 

 the Ca ++ -K+ ratio is the significant quantity in deter- 

 mining central nervous system excitability, son Euler 

 (154) also obtained an elevation of arterial pressure 

 in the cat following intracisternal injection of K.C1 

 and reported that calcium had little effect, although 

 it neutralized the action of potassium. Similar results 

 had been reported by Resnik et al. (125) following 

 intracisternal administration of K.C1 in clogs, with the 

 exception that very slight concentrations of potassium 



lowered the arterial pressure. Walker et al. (156) con- 

 cluded that potassium produces a general stimulation 

 of the central nervous system, contrary to Stern & 

 Chvoles (140) who believed that the sympathetic 

 centers are stimulated while the parasympathetic are 

 depressed. 



Leusen (100) agrees with the interpretation of 

 Walker et al., on the basis of his studies with pertusion 

 of the cerebral ventricles in dogs after vagotomy and 

 carotid sinus isolation. He found that an excess of 

 potassium in the perfusate of the cerebral ventricles 

 raised the arterial pressure and enhanced the vaso- 

 motor reflexes whereas perfusion of the cerebral 

 ventricles with a potassium-free solution had no effect 

 on these indices. An excess of calcium or magnesium 

 in the perfusate caused a depression of the arterial 

 pressure and of the vasomotor reflexes. 



Sabbatini in 1001 (131) clearly demonstrated the 

 importance of the calcium ion concentration on the 

 .ictivitv of the cells of the central nervous system. By 

 comparing the gro-s effects produced by lowering the 

 calcium of the blood serum ((141 with those produced 

 by the injection of sodium citrate into the cisterna 

 (84), it could be inferred that the calcium ion concen- 

 tration in the cerebrospinal fluid is of far greater 

 importance for the production of peripheral neuro- 

 muscular symptoms than is the calcium ion concentra- 

 tions of the blood serum. 



In this regard, Rubin et al. (130) recorded the 

 cortical electrogram and tin- simultaneous electro- 

 cardiogram of cits during the intravenous injection 

 of salts of potassium, calcium and magnesium. Potas- 

 sium and calcium produced no changes in the cortical 

 electrogram until the development of intraventricular 

 block or of cardiac arrest, at which time slowing of 

 tin- cortical electrogram developed. Magnesium, how- 

 ever, produced transient periods of slowing before 

 pathological changes appeared in the electrocardio- 

 gram. This immunity of the central nervous system to 

 drastic changes in blood concentrations of K. + and 

 Ca -1-1 ", compared with its sensitivity to alterations in 

 cerebrospinal fluid concentrations of these cations, is 

 a further dramatic illustration of the homeostatic 

 regulatory mechanism resident in the blood-brain 

 barrier. 



When the calcium concentration of the cerebro- 

 spinal fluid was lowered, either by repeated with- 

 drawal of cisternal fluid and its replacement w r ith 

 calcium free cerebrospinal fluid or by intracisternal 

 injection of sodium citrate, there resulted a marked 

 increase in muscular activity which could be easily 

 detected before any marked change in arterial pres- 



