GENERAL COMMENTS 155 



change in its functioning. Thus, the decrease in the levels of 

 phosphocreatine induced by convulsants such as metrazole or by 

 partial or complete anoxia, have been correlated with changes in 

 the electrical activity of the cortex and have shown that the meta- 

 bolism of phosphate derivatives is amongst the first detectable 

 major biochemical events associated with such changes. Experi- 

 ments with intact animals do not permit detailed studies of this 

 type but nevertheless have provided confirmatory evidence that the 

 changes noted do in fact take place as a result of procedures 

 stimulating the brain. On the other hand changes induced by 

 emotional excitation can be studied only in conscious animals. The 

 ability to link a biochemical change with a functional change in the 

 brain in vivo makes it appropriate that the study of new phenomena, 

 the appraisal of diff"erent techniques, or the determination of 

 quantities of new compounds should first be investigated at this 

 level of tissue organization to provide the basic information 

 necessary to further investigation with other preparations of 

 brain. 



It must be noted however that the nature of the technique 

 involving freezing of almost the whole brain, permits as yet only a 

 study of gross effects and the examination of details of metabolism 

 is difficult. For example, only one experimental figure can usually 

 be obtained from one animal, which can lead to considerable 

 variability in the data, and the fixation of the brain in liquid air is 

 not an immediate process, which renders difficult investigations 

 of relative speeds of reaction. The use of radioisotopic phosphorus 

 and other intermediates appears to offer little solution of some of 

 these problems. Though intracisternal injection leads to a rapid 

 accumulation of appreciable radioactivity the rate of entry into all 

 parts of the brain is not uniform, and at the best, values calculated 

 for metabolic rates can only represent a bottom limit for the actual 

 rate of metabolism. It is therefore not altogether surprising that 

 w^ork in vivo has centred upon prhosphates such as adenosine 

 triphosphate, phosphocreatine, phosphoprotein and the cephalin 

 diphosphoinositide, all of which incorporate radioactive phosphate 

 to a marked extent in vivo. While this defect has perhaps operated 

 advantageously in focusing attention upon those phosphates 

 which are metabolically the most active, it serves to detract from 

 others, such as certain of the phospholipids, whose apparent 

 stability may be equally important to the normal functioning of the 



