METABOLISM IN THE NORMAL FUNCTIONAL STATE 19 



cisternal injection therefore does not bypass any barrier but is 

 simply a useful technique for rapidly presenting the brain with a 

 high concentration of radioactive phosphate. Much of this 

 phosphate is rapidly lost to the blood (Sacks and Culbreth, 1951 ; 

 Strickland, 1952) though this has been denied (Lindberg and 

 Ernster, 1950). 



Certain areas of the brain appear to be relatively unprotected by 

 a blood-brain barrier when compared with other areas as judged 

 by the apparent entry of phosphate when injected into the blood- 

 stream. In the human subject following intravenous injection of 

 radioactive phosphate, radioactivity was found to be greatest in the 

 thalamus and hypothalamus, while in the rabbit and rat radio- 

 activity was greatest in the pituitary, pineal gland, choroid plexus 

 and hypothalamus (Bakay, 1951, 1953; Bakay and Lindberg, 1949; 

 Borell and Ostrom, 1945). It was suggested by Borell and Ostrom 

 (1945) that the greater uptake of phosphate by the pituitary is a 

 reflection of the high expenditure of energy involved in the syn- 

 thesis of hormones. It is difficult to see how such an explanation 

 could hold for the pineal gland. More probably an apparently 

 greater uptake of phosphate in certain areas of the brain is a reflec- 

 tion of the degree of vascularity of that particular area and of the 

 connexions existing, as in the case of the pituitary (Daniel et al., 

 1958), with the main blood stream. It should also perhaps be 

 emphasized that all experim.ents of the type described above using 

 radioactive phosphate simply measure the exchange of radio- 

 activity across a membrane and do not measure amounts trans- 

 ported into the brain. 



hicorporation of Radioactive Phosphorus into the Acid-soluble 

 Phosphates 



Although analytical data of the type given above showed that 

 brain contained many phosphates known to be rapidly metabolized 

 in normal cellular processes, direct evidence upon the rate of such 

 metabolism in the brain in vivo is still lacking. Attempts to 

 provide such data for the acid-soluble phosphates have been made 

 by Bakay and Lindberg (1949), Lindberg and Ernster (1950) and 

 Zetterstrom and Ljungren (1951). When radioactive phosphate 

 was injected into rabbits by the intracisternal route it was found 

 that phosphates soluble in trichloracetic acid became radioactive 

 much more rapidly than those that were insoluble. Analysis of this 



