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HANDBOOK OF PHYSIOLOGY 



NEt ROPHYSIOLOGY III 



may instance the knowledge of the part played by 

 pyruvic acid, which lias now led to clinical tests in 

 the blood for bcri beri and other conditions. Much of 

 this work, however, has now passed into history, and 

 there is an increasing interest in the whole field of 

 lipids and their dynamic interchanges. At the same 

 time, the progress of pharmacology has given us sub- 

 stances of great activity when presented to nervous 

 tissue in minute amounts; we may mention 5-hydroxy- 

 tryptamine. More important still, the writer feels, is 

 the development of micromethods of enzyme analysis 

 in Chicago by Lowry where pioneer studies in micro- 

 methods of the Copenhagen school led by Linder- 

 streSm-Lang are being applied to the nervous system. 

 When these can be combined adequately with elec- 

 tron microscope pictures, we may then be able to 

 start upon our final analysis of events. Already we 

 know that there is a pharmacological connection be- 

 tween activity and the events concerned with acetyl- 

 choline. Further, it is clear from some of the work 

 with vitamin-B deficiencies and with toxic substances 

 that the background enzyme activity can be rather 

 direct!) related to convulsive states. At the same 

 time we must not expect that studies in vitro can 

 give us the final and predominantly important subtle- 

 ties which must depend upon the whole intact tissues 

 with their full organization. Indeed, as the contents 

 of this book show, it is still not possible to pick up 

 experimentally metabolic changes accompanying 

 mental activity. The central nervous system too is 

 additionally protected against changes in its external 

 chemical environment by the so-called blood-brain 

 barrier. 



In .1 survey of what lies before us, it may be that 

 we ought to follow the example of the astronomers 

 who for some [50 years have been planning ahead 

 foi their successors. The time scale of their events 

 and the cost of their equipment doubtless made this 

 necessary. In our case it is true that new techniques 

 are continually arising and that this would mean a 

 constant revision of am scheme; but at the same 

 time, some degree of international planning which 



was not restrictive might help some pluses of the 



work. The sheer economics of mental illness almost 

 imposes exploration of even possible approach. In 

 anv rase the note of patience must be sounded again. 

 Ii will take time to understand it all properly from 

 whatever angle the approach is made, but h can be 

 predicted with complete confidence that when we do, 

 the practical applications in medicine will follow 

 rapidly, and that even partial solutions will be better 

 than empiricism. 



This volume of essays on various aspects of the 

 modern picture must therefore be regarded as a 

 volume of milestones in our approach to the final 

 goal of an understanding of neurophysiology inter- 

 preted in the widest sense. To those in the "trenches' 

 of medicine much of it must seem to be remote, and 

 indeed much will be superseded with newer observa- 

 tions, but even if 10 per cent remain, it is a truism to 

 point out that this is an important advance in knowl- 

 edge. The Editors have arranged so that the subject 

 is well covered. The chemical background is given 

 attention in neural chemistry and metabolism, and 

 the more dynamic aspects in neuronal metabolism. 

 A large amount of strictly biochemical work in vitro 

 is well reviewed in central nervous system metabo- 

 lism in vitro, and the same extensions of this in vivo 

 are then set forth. To complete the picture, separate 

 chapters have been devoted to the effect on neural 

 function of changes in cellular metabolism and then 

 to abnormalities induced by the presence of cither 

 nutritional deficiencies or of congenital disorders. 

 One should underline here the astonishing brain 

 disturbances induced by thiamine deficiency and in 

 the pellagra induced by nicotinic acid deficiency. 

 They are not so surprising when we remember the 

 general sloth and hallucinations which occur in 

 hypothyroidism, or the effects of hypoglycemia fol- 

 lowing the overdose of insulin. It is still not clear 

 why glucose is almost unique in stopping insulin 

 convulsions. Perhaps this is related to recent work in 

 Rome upon the increase in glycogen concentration 

 in rat diaphragms induced by insulin. 



The Editors had in mind a contribution to the 

 understanding of the relations between metabolism 

 and function, questions of the most far-reaching im- 

 portance because they involve a decision as to the 

 extent to which the metabolism only maintains the 

 structure and the extent to which it contributes to 

 the working functions. The writer thinks that a pe- 

 rusal should convince vis that it is now no longer ad- 

 visable to take the view of some older physiologists 

 ih.it one can separate the point of view of the bio- 

 chemists and the physiologists. According to this (and 

 it was reasonable al the time), phv siologists could 



accept the idea <>l the central nervous swem as a 

 normal working system, relegating the constitution 

 of the substances being investigated largely to the 

 role of excretion and other such biochemical proc- 

 esses. At least it must be clear now that the biochem- 

 istry does and must often actively intrude even in 

 physiological experiments. In this region ol metabo- 

 lism we are beginning to see some connection between 





