METABOLISM OF THE CENTRAL NERVOUS SYSTEM IN VIVO 



>8 5 5 



energy utilization. There is also a decrease in the 

 concentration of ammonia (143) and an increase in 

 the acetylcholine level (142) in the brain. In the 

 mouse brain during pentobarbital anesthesia, a 

 reduction in the rates of synthesis of nucleoprotein 

 and phospholipids also has been observed (28). 

 Comparable changes in these various brain con- 

 stituents have been observed to occur with changing 

 physiological conditions. Thus, in rat brains lactic 

 acid (144) was found to be reduced and acetylcholine 

 (142) increased during natural sleep, while durint; 

 excitement reverse changes occurred. Phosphate 

 esters were little affected during either sleep or ex- 

 citement (144). In general, the changes in brain 

 constituent concentrations which are associated with 

 altered cerebral activity follow the patterns to be 

 expected from the altered energy demands of the 

 functional states, increased and decreased activity 

 giving evidence of increased and decreased rates of 

 glycolysis and high-energy phosphate bond degrada- 

 tion, respectively. 



Effects of Attend Body Temperature on 

 Cerebral Metabolic Rate 



Studies in animals clearly demonstrate thai 



cerebral oxygen consumption is reduced when 

 significant lowering of body temperature, for example 

 below 30°C, is achieved by lowering the environ- 

 mental temperature (50, 106, 150). In one of these 

 studies in dogs with body temperatures between 

 22°C and 27°C (106), cerebral blood flow was found 

 to be so reduced, perhaps because of the increased 

 viscosity of the blood, that despite the depressed 

 metabolic rate, a relative cerebral ischemia and 

 anoxia was present. The cerebral respiratory quotient 

 (R.Q. ) remained unchanged. In .mother study in 

 hypothermic dogs both cerebral blood flow and 

 oxygen consumption fell linearly and proportionately 

 to levels at 26°C, equal to approximately one third 

 of normal (150). There was, therefore, no evidence 

 of cerebral anoxia. In cats cerebral oxygen consump- 

 tion falls even more rapidly in hypothermia than 

 does blood flow, clearly indicating a primary reduc- 

 tion in cerebral metabolic rate (50). The effects of 

 lowered body temperature in man have not yet been 

 reported. 



The results of studies on the effects of increased 

 body temperature are still somewhat confusing. A 

 rise from 24°C to 34°C in the environmental tempera- 

 ture of one-day-old rats, which are poikilothermic, 

 reduces their survival time under anoxic conditions 



to less than half (36), evidence of an increased demand 

 for oxygen at the elevated temperatures. No such 

 effect is observed in the adult rat which, however, is 

 homoiothermic and probably maintains a normal 

 body temperature under such conditions. In neuro- 

 syphilitic adult man, Himwich and co-workers (77) 

 found an increase in arteriovenous oxygen difference 

 during fever induced by the inductotherm, or the 

 injection of typhoid vaccine or malarial parasites. 

 Looney & Borkovic (119) found no such change in a 

 similar group of patients treated with hyperpyrexia. 

 The only quantitative study reported thus far in 

 man is that of Heyman and associates (74) who found 

 in both asymptomatic and symptomatic neuro- 

 syphilitic patients treated with fever therapy no 

 significant increase in either cerebral arteriovenous 

 oxvgen difference or cerebral oxygen consumption 

 with increased body temperature. However, since 

 neurosyphilis can be associated with cerebral meta- 

 bolic abnormalities as indicated by the depressed 

 cerebral metabolic rate in the symptomatic patients 

 (138), it would be of interest 10 repeat such studies in 

 normal man. 



METABOLISM OF MIL CENTRAL NERVOUS S\ s i i \i 

 IN VARIOUS PATHOLOGICA1 STATES 



Much of our present know ledge of the metabolism 

 of the central nervous system is derived from ob- 

 servations in functionally abnormal states, and many 

 of these observations have been made in man. In 

 table 3 are tabulated some of the results obtained in 

 studies of the human cerebral metabolic rate in 

 various pathological states, some occurring spon- 

 taneously, others artificially induced by pharma- 

 cological agents. All are characterized by clear 

 evidence of mental and, therefore, cerebral dysfunc- 

 tion. It can be seen that those conditions which 

 exhibit alterations in cerebral metabolic rate can be 

 readily classified according to the general nature of 

 the cerebral metabolic defect. 



Inadequate A utrient Supply 



circulatory deficiency. The effects of reduction of 

 cerebral blood flow upon brain metabolism in ex- 

 perimental and clinical conditions have been described 

 in a previous part of this chapter. It may be added 

 that prolonged impairment of the cerebral circula- 

 tion produced, for example by cardiac arrest, rapidlv 

 leads to irreversible intracellular metabolic changes 



