56 METABOLISM IN CHANGED CEREBRAL ACTIVITY 



without the compHcations of an added hypoxia. Animals are 

 anaesthetized and the skull opened, and after immobilization with 

 dihydro-j8-erythroidine are maintained with artificial respiration. 

 Study of the electrocorticogram during the experiment enables 

 the selection of a point at which convulsive electrical activity 

 occurs following suitable stimulation, when the brain is then frozen 

 with liquid nitrogen. With this technique it has been found that 

 phosphocreatine decreases and inorganic phosphate increases 

 during a seizure, the levels of adenosine triphosphate remaining 

 reasonably constant (Table 10). 



Provided the oxygen tension remains adequate the extent to 

 which phosphocreatine decreases appears to be determined by the 

 severity rather than by the duration of the convulsive discharge. 

 Thus, in the dog (Table 11) during convulsive activity induced by 

 metrazole the quantities of phosphocreatine, after an initial change, 

 did not decrease further over a period of 2J min. However if the 

 seizures were of the grand mal type phosphocreatine decreased 

 further to levels of 1-9 ju,moles/g. Parallel with such changes levels 

 of cerebral glucose decreased and those of lactic acid increased 

 indicating that the changes in the labile phosphate were accom- 

 panied by an increase in cerebral metabolism. Throughout the 

 convulsive discharge the arterial oxygen tension remained normal. 

 In prolonged convulsions the increased inorganic phosphate 

 appears to find its way into the blood, for in dogs examined with 

 the above technique convulsive activity was associated with an 

 increase in the acid-soluble phosphate in blood from the superior 

 sagittal sinus but not in femoral blood (Cicardo, 1945). 



The speed with which a change in phosphate levels can occur 

 following administration of a convulsant is well illustrated by the 

 experiments of Dawson and Richter (1950Z)). Unanaesthetized 

 rats were given electroshock via cerebral electrodes during or after 

 which they were drowned in liquid nitrogen. Animals drowned 

 within 1 sec of applying the shock had suffered a loss of 50% of 

 their cerebral phosphocreatine with the final level not decreasing 

 further as a result of continuing the shock for another 5 sec. 

 Allowing for the time taken to freeze the entire brain (about 4 sec) 

 the speed of breakdown can be calculated to be between 1000 and 

 3600 ^moles phosphorus/g wet wt. hr~^, a rate considerably in 

 excess of any known energy-consuming reactions in the brain. 



A reasonable interpretation of the changes described above is in 



