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a considerable degree of autonomy. However, it is 

 of interest to examine the relationship of the small 

 degree of variability of cerebral metabolism to its 

 own physiological state and that of the rest of the 

 bod) . 



Relationship of Cerebral Metabolism to Circulation 



As is true in all tissues, the purpose of the cerebral 

 circulation is to suppl) the brain with essential nu- 

 trients and tn remove the products of its metabolism. 

 As long as blood Bow is adequate to perform these 

 functions, it lias no influence on the metabolic rate. 

 Under normal conditions, metabolic rate is never 

 limited by the blood flow, ,md increasing the blood 

 flow does not alter thai rate (92, 101). The rates of 

 exchange of metabolites between brain and blood 

 remain the same; the arteriovenous differences merely 

 decrease in proportion to the increase in blood flow. 

 When blood flow is reduced in the presence of a 

 constant metabolic demand, the reverse occurs, and 

 the arteriovenous differences increase proportionate!) 

 until a limit is reached beyond which the brain no 

 longer is able to extract adequate amounts of nutrient 

 material to support its metabolic needs. This limit is 

 quite low as indicated by the studies of Finnerty and 

 co-workers (46) who found that cerebral blood flow 

 could be reduced by drug-induced arterial hypo- 

 tension to approximately 60 per cent of the normal 

 value or to the point of fainting without any measur- 

 able decrease in the cerebral oxygen consumption. 

 Eventually, however, the cerebral metabolic rate can 

 be reduced by a deficient circulation as in secondary 

 shock (42) or in conditions of markedly increased 

 intracranial pressure (102), sometimes to a level so 

 low thai unconsciousness ensues. It is only under such 

 conditions that raising the rate of blood flow increases 

 the metabolic rale. When such a phenomenon occurs, 

 it is pathognomonic oi tissue ischemia, and any ex- 

 perimental preparation in which it occurs, as for 

 example the perfused 1. it brain employed by Geiger 

 and co-workers 1 ",1 I, must be suspected oi this serious 



delect. 



Although cerebral metabolic rate can be main- 

 tained independent of the blood flow over .1 wide 

 range, in normal circumstances it is probabl) not 

 exposed to extremes of blood flow, Homeostatic 

 mechanisms exisl which adjust the cerebral blood 

 flow to the metabolic demands and so to the func- 

 tional activit) of the brain. I In mechanisms achieving 

 this regulation are discussed b) Schmidt in Chapter 

 LXX and b) Kety in ( Ihapter I .XXI in this Handbook 



Relationship oj Cerebral Metabolism 

 in Growth, Development and Age 



In figure 1 is presented a modification of the graph 

 constructed by Kety (93, 94) from the data obtained 

 in various laboratories illustrating the effect of aging 

 on the rate of cerebral oxygen consumption in normal 

 man. The modification consists of the inclusion of 

 data from two recently reported studies (132, 175; 

 Sokoloff, Dastur, Lane & Kety, unpublished obser- 

 vations!. It is seen from figure 1 that cerebral meta- 

 bolic rate in normal subjects is high in childhood, 

 presumably during growth and development of the 

 brain, decreases most rapidly until puberty or mid- 

 adolescence, falls more slowly between puberty and 

 early adulthood, and then remains relatively constant 

 thereafter into senescence. The previous belief that 

 cerebral metabolic rate normally falls progressively 

 throughout the life span arose from inclusion in the 

 older groups of patients with various vascular and 

 nervous diseases commonly associated with aging 

 in which cerebral oxygen consumption has been 

 found to be reduced (41, 48, 115, 169). This is prob- 

 ably the reason for the obvious disparity of the two 

 lowest points in figure 1 which were obtained in 

 hospital patients not as rigorously screened for nor- 

 mality (37, 43) as in the other studies. 



The three youngest groups represented in figure 1 

 are from the studies of Kennedy and co-workers 

 (87, 88). Their values for cerebral metabolic rate in 

 the first decade of life are considerably higher than 

 those obtained by Baird & Garfunkel (6) whose 

 results indicated the same cerebral oxygen con- 

 sumption in childhood as in adulthood. However, 

 their subjects included patients with neurological 

 disease, mental deficiency and similar conditions 

 which could be responsible for a reduced cerebral 

 metabolic rate and are, therefore, probably not 

 representative of the normal state. If the data of 

 Kennedy and associates are trul) representative, 

 then the cerebral oxygen consumption in the middle 



ol the first decade of life can account for as much as 

 50 per cent of the total basal bod) owgen consump- 

 tion (87). 



Relationship between Metabolic R<it< and Functional 

 Activity in the Central Nervoui System 



In organs Mich as the heart or skeletal muscles 

 which perforin mechanical work, increased functional 



activit) is clearl) associated wiih increased metabolic 



rate. In nervous tissues outside the central nervous 



