156 GENERAL COMMENTS 



brain. In spite of these limitations, comparison of different treat- 

 ments made in a standardized manner is possible provided 

 suitable bases for comparison are chosen (see pp. 22-29). 



Preparations of cerebral tissue in vitro permit a more detailed 

 examination of the metabolic potential of the tissue but here also 

 problems arise when cellular structure is disrupted. Intact 

 cerebral slices retain many characteristics of the whole brain, 

 amongst which the ability to respond metabolically to applied 

 electrical stimulus, or to increased concentrations of potassium 

 salts, is lost upon disintegration. Investigations of the relationships 

 between metabolic changes and physical stimuli are therefore 

 limited at present to the intact cell containing tissue. Nevertheless, 

 the examination with such preparations of a wide variety of agents 

 known to effect cerebral metabolism and function in vivo, has 

 provided the closest parallels yet found between changes taking 

 place in vivo and those in vitro. It has permitted the study both of 

 the linkages between phosphate metabolism and applied stimulus 

 and of the effects of therapeutic agents upon such metabolism. 

 This type of study is not possible with disintegrated preparations 

 which offer advantages over intact cerebral slices in the elucidation 

 of synthesis and degradation and of the interactions of the various 

 cellular constituents with one another. Choice of the level of tissue 

 organization at which work is carried out is thus governed by the 

 nature of the problems to be studied. Ideally, a problem is 

 investigated at all three levels, though rarely by the same group of 

 workers. 



Speed of Change of Labile Phosphates 



Possibly the most striking feature of phosphorus metabolism in 

 the brain is the rapidity with which the levels of phosphocreatine 

 and inorganic phosphate change in response to an applied stimulus. 

 The rate of change of phosphocreatine in vivo has been calculated 

 to be between 900-3000 jixmoles/g hr-^; experiments in vitro sug- 

 gest a more probable figure of 1500 jitmoles/g hr*^. The break- 

 down of phosphocreatine almost certainly precedes any event 

 such as the increase in oxygen uptake which also follows a 

 stimulus, and places changes in phosphate metabolism amongst the 

 primary events involving a change in cerebral activity. It has also 

 been shown that levels of adenosine triphosphate decrease markedly 

 before changes in levels of phosphocreatine commenced. This 



