48 METABOLISM IN CHANGED CEREBRAL ACTIVITY 



Early work in the dog (Kerr and Ghantus, 1936) indicated that 

 hypoglycaemia induced by insuHn was without effect upon the 

 quantities of phosphocreatine in the brain. In these experiments, 

 however, the animals were anaesthetized after giving insulin so as 

 to facilitate removal of the brain. It seems likely that this procedure 

 would permit the resynthesis of phosphocreatine to normal levels 

 before analyses were begun. Later, Olsen and Klein (1947) 

 working with cats anaesthetized and maintained by artificial 

 respiration, found that the levels of cerebral phosphocreatine 

 decreased as the severity of the hypoglycaemia increased ; changes 

 were from normal value of 2-4 /xmoles/g wet wt. to a final value of 

 0-9-1 -4 /xmoles/g wet wt. in hypoglycaemic coma. These decreases 

 were also accompanied by a fall in levels of adenosine triphosphate 

 and a rise in levels of inorganic phosphate. 



Hypoglycaemia, when induced in the rat by insulin, was found 

 to increase the specific radioactivity of the acid-soluble phosphates 

 of brain, relative to that in the blood, by some 15-20% over that in 

 the normal control animals. Nevertheless the exchange of phos- 

 phorus between the acid-soluble phosphates and the phospholipids 

 was markedly decreased (Dawson and Richter, 1950a). These 

 results imply either that the rate of turnover of the acid-soluble 

 phosphates is decreased or that the metabolism of the phospho- 

 lipids becomes predominantly catabolic in the absence of a normal 

 glucose supply. Although evidence for the former does not appear 

 to be available, evidence for the latter has been provided. Pro- 

 longed insulin hypoglycaemia was found to decrease the total 

 quantities of phospholipid phosphorus of rabbit brain (Randall, 

 1940; McGhee et al. 1951) a decrease which was apparently 

 irreversible and could not be restored when lecithin or glucose were 

 administered even in large amounts. Similar changes have been 

 described by Geiger and co-workers. Thus it was found that 

 during perfusion of the isolated head of the cat with a modified 

 " blood " free from glucose, the respiratory quotient of the brain 

 decreased from a value of 1-0 at the start to about 0-5 though the 

 oxygen consumption remained high (Geiger et al, 1952). Accom- 

 panying this decrease there was a loss of phospholipids, phospho- 

 proteins and nucleic acids from the tissue. Catabolism of these 

 appears to be selective since the major losses occurred in the 

 particles in the microsomal fraction and not in the mitochondria 

 (Abood and Geiger, 1955). These changes did not occur if 



