METABOLISM OF THE CENTRAL NERVOLS SYSTEM IN VIVO 



.849 



table 2. Relationship between Oxygen and Glucose Metabolism in Normal Young Adult Human Brain 



* Calculated from median values reported in table 1 . 



t Calculated on basis of 6 moles of oxygen required for complete oxidation of 1 mole of glucose, 



Evidence for Obligatory Aerobic I 'tilirjition of 

 Glucose by the Central Nervous System 



The fact that the central nervous system under 

 normal circumstances derives its energy from the 

 oxidation of glucose does not reveal the entire picture 

 of the uniqueness of its metabolism. In the normal 

 state when all possible substrates arc available, it 

 may simply reflect the preferential metabolic path- 

 ways. However, the available evidence at present 

 strongly indicates that the aerobic utilization of 

 glucose is not a preferential pathway but an oblig- 

 atory one for the maintenance of normal function. 

 The available stores of oxygen and glucose within 

 the central nervous tissues are so small compared 

 with their rate of consumption that the functions 

 of the nervous system are completely dependent on 

 their constant uninterrupted renewal by the circula- 

 tion. Complete cessation of the cerebral circulation 

 in man, for example, results in the loss of consciousness 

 within 10 sec. (151), the approximate interval of 

 time required to utilize the estimated stores of oxygen 

 within the brain (92). Since the stores of glucose 

 and glycogen within the brain are relatively greatei 

 than that of oxygen (89, 90, 92), the acuteness of this 

 effect is almost certainly the result of a deficiency 

 of oxygen rather than of glucose. Furthermore, the 

 well-known effects of anoxia or anoxemia on cerebral 

 functions leave little doubt of the essential nature of 

 oxidative metabolism for the maintenance of these 

 functions. (These effects are discussed also by Tschirgi 

 in the subsequent chapter in this volume.) 



The evidence that normal function in the nervous 

 system is dependent upon the obligatory consumption 

 of glucose is derived mainly from three groups of 

 in vivo observations. 



IMPAIRMENT) OF CENTRAL NERVOUS SYSTEM VIIVIIY 

 PRODUCED BY (.1 I < 1 isE DEPRIVATION. It is well know 11 



tli.it in man a fall in blood glucose concentration is 

 associated with changes in mental siate ranging from 

 mild subjective sensory disturbances to coma. (See 

 also Tschirgi's account of hypoglycemic effects in 

 the following chapter in this volume.) The degree of 

 functional or behavioral impairment is well corre- 

 lated with the degree of hypoglycemia (20, 81, 103, 

 118, 122). Abnormalities in the electroencephalogram, 

 for example increasing prominence of delta rhythms 

 1 id, _>4, 81, 831 and reductions in the cerebral arterio- 

 venous oxygen difference (75, 76, 78, 80, 103, 198) 

 and oxygen consumption (103), increase with de- 

 creasing blood glucose levels. According to K.ety 

 and co-workers 1 1 o ; 1, vv hen the arterial blood glucose 

 level was reduced from a normal level of 70 to 100 my 

 per cent to a mean value of l<) mg per cent, schizo- 

 phrenic patients given insulin became confused and 

 the mean cerebral oxygen consumption fell to 2.6 

 ml per 100 gm per min. or 79 per cent of the normal 

 level. At an arterial glucose level of 8 mg per cent. 

 deep coma ensued and cerebral oxygen consumption 

 decreased further to 1.9 ml O-. per 100 gm per min. 

 1 hese changes occurred despite a slight increase in 

 cerebral blood flow In the state of coma the cerebral 

 glucose utilization was negligible, 0.8 mg per 100 gjrn 

 per min. Animals exhibit similar behavioral and 

 electroencephalographic changes during hypogly- 

 cemia (120, 123). Although in most of the reported 

 studies hypoglycemia was produced by insulin ad- 

 ministration, the described changes cannot at present 

 be attributed to a direct action of insulin on the 

 central nervous system. First, the degree of altered 

 function is correlated with the degree of hypoglycemia 

 and not the insulin dosage. Secondly, the admin- 



