412 CLEMENTE AND RICHARDSON 



Gangloff and Haley, 1960), and we have little information of subtle changes 

 that radiation can produce in neuronal function or of neurochemical obser- 

 vations. 



We would like to slant this report away from the direct effects of radia- 

 tion on the neuron and examine more closely our research results, and those 

 of other investigators, on the cerebral capillary and neuroglial systems. This 

 we feel has an important place in such a conference because it has been 

 shown that brain radiations can result in edema and inflammatory reactions 

 around cerebral capillaries and because neurons are elaborately sensitive to 

 ionic and other chemical changes in their environment; their functional in- 

 tegrity can be altered by the slightest alteration in its metabolic medium. 



The Concept of the Blood-Brain Barrier 



That a selective barrier exists between certain circulating elements in the 

 blood stream and brain tissue has been known since Ehrlich (1885) found 

 that the brain remained unstained following the intravenous injection of 

 acidic dyes, which brilliantly stained most of the other organs. This peculiar- 

 ity in regard to the central nervous system has given rise to the concept of 

 the existence of a blood-brain barrier, and in general it is observed that 

 transvascular permeability characteristics tend to be manifested by a slower 

 exchange rate of substances passing between blood and brain (in com- 

 parison to other organs) rather than a faster rate of exchange. 



The acidic aniline dye, trypan blue, has been classically used by many in- 

 vestigators to demonstrate the blood-brain barrier phenomenon. More re- 

 cently, certain radioactive tracers (notably P'-, Br--, and Na^*) have been 

 used. Although the use of dye techniques has been valuable in the formula- 

 tion of the barrier concept, these methods are not above criticism. It should 

 be pointed out that acidic dyes (such as trypan blue) tend to bind more 

 completely with plasma proteins than basic dyes, which tend to stain brain 

 structines following systemic administration ( Bennhold, 1932). Were we to 

 depend on dye studies alone, it could be argued that the blood-brain barrier 

 is merely a display of the impermeability of the cerebral vasculature to 

 plasma proteins, a reasonable and predicable situation. 



With the advent of radioactive tracer methods, however, it has been shown 

 that following the systemic injection of certain ions the ti'acer becomes dis- 

 tributed throughout all the organs of the body uniformly and rapidly, 

 whereas the relative concentration of the tracers in the brain are significantly 

 lower (Manery and Bale, 1941; Greenberg et al., 1943; Wang, 1948). 

 Although the rate of passage of radioactive tracers from blood to brain 

 differs with respect to the particular ion being studied, curves can be ob- 

 tained which reveal the amoimt of tracer in the brain at any given time 



