METABOLISM OF THE CENTRAL NERVOUS SYSTEM IN VIVO 



1845 



stance in the tissues of the nervous system. For ex- 

 ample, C 14 -labeled lysine has been thus employed in 

 mice to determine the half life of free lysine and lysine- 

 containing proteins of the brain (107). A similar 

 approach has been used to study the effects of pento- 

 barbital anesthesia, electrically induced convulsions 

 and insulin hypoglycemia on the rate of incorporation 

 of radioactive phosphorus (P 32 ), administered as 

 phosphate, into the phospholipids and nucleoproteins 

 of the mouse brain (28). 



This group of methods, particularly those utilizing 

 radioisotope tracer techniques, is a valuable ad- 

 dition to the armamentarium for studying central 

 nervous system metabolism in vivo. They permit under 

 more or less physiological conditions quantitative 

 investigations of the intermediary metabolism not 

 presently possible by any other in vivo techniques. 

 On the other hand, they are subject to the usual 

 restrictions imposed by the blood-brain barrier, 

 they are, therefore, limited to materials which can 

 penetrate into the nervous tissues from the blood or, 

 in some cases, the spinal fluid. They require reliable 

 data on the content of the blood within the tissue 

 studied so that proper correction for the contribution 

 by the blood to the quantity of radioactivity or 

 metabolite, or both, found in ihe tissue can be made. 

 Finally, they require the sacrifice ol the animal for 

 each experiment. 



Arteriovenous Different es 



Substances exchanged between central nervous 

 system tissues and blood are present in different 

 concentrations in arterial and venous bloods. For a 

 steady state of blood flow, the arteriovenous difference 

 is directly proportional to the rate of utilization or 

 production of the metabolite l>v the tissue. 



This technique has been the basis of some of the 

 earliest studies of cerebral metabolism in man (20, 1 16, 

 117) in whom it can be employed without anesthesia 

 and where, because of a favorable vascular anatomy, 

 it is most readily applicable. Arterial blood can be 

 obtained from any artery, but the venous blood 

 presents special problems. It must be representative 

 of the mixed venous drainage of the tissue under 

 study; otherwise, it represents undefined areas of that 

 tissue. It must also be relatively uncontaminated by 

 blood from tissues other than the one under study. 

 These requirements are satisfactorily achieved in 

 man by sampling of cerebral venous blood from the 

 superior bulb of the internal jugular vein by the 

 technique of Myerson el al. (133). Blood thus drawn is 



representative of the brain as a whole and contains 

 only three per cent contamination from extracerebral 

 sources (168). In the common laboratory animals, 

 except for the monkey, the anatomy of the cerebral 

 circulation is such that extensive communications 

 between cerebral and extracerebral venous blood 

 occurs (7). It is, therefore, generally difficult without 

 major surgical intervention to obtain suitable repre- 

 sentative cerebral venous blood samples. Such studies 

 have, however, been carried out in lower animals, 

 but they are usually of questionable specificity. 



The advantage of this method lies in its relative 

 simplicity and its applicability to unanesthetized man. 

 Since arteriovenous differences depend not only on 

 metabolic rate but on blood flow as well, they do not 

 yield quantitative data on rates of utilization or 

 production. They do, however, give information on 

 the direction and relative rates of utilization or pro- 

 duction of those metabolites which pass the blood- 

 brain barrier. Moreover, comparisons of rates of 

 utilization or production among various metabolites 

 are possible, as, lor example, the comparison of the 

 oxygen and carbon dioxide arteriovenous differences 

 in the determination of the cerebral respiratory quo- 

 tient in run. 



Combination »/ Blood Flou and , Irtt not - nout Differt m < 1 



By combining the measurment of blood How with 

 the determination of arteriovenous concentration 

 differences, the rates of utilization or production of 

 specific metabolites can be quantitatively estimated. 

 I hese rates are simply the products of the values for 

 blood How and arteriovenous difference. Ihe methods 

 for the measurement of blood How in the central 

 nervous svsteni have lor the most part been applicable 

 only to the brain, and even here most of them are 

 open to set ions criticism (66). (They are discussed 

 by Ketv in Chapter LXXI of this Handbook I 



Perfusion methods have been employed in studies 

 on the entire head (15), the whole isolated brain 

 (18, 51), portions of the cerebral cortex (67) and 

 parts of the spinal cord (190), sometimes in associ- 

 ation with a flow-meter device to measure the rate 

 of flow of the perfusate, or of blood during natural 

 perfusion of the brain by the animal's own circulation. 

 These devices include the rotameter (66, 150), 

 thermoelectric devices (57, 66) and the bubble-flow 

 meter (31, 66). One of these, the thermoelectric 

 flow recorder (57), is designed in the form of a needle 

 which when inserted into the jugular vein of man has 

 been capable of yielding relative values for human 



