418 CLEMENTE AND RICHARDSON 



central nervous system. In light of the fact that morphologic changes in 

 cells and fibers at these low dose levels are unobservable, perhaps the func- 

 tional alterations observed are the result of an altered neuronal milieu or 

 changes in the ionic medium of neuronal pools which may be transient at 

 lower doses or may result in neuronal damage or neuron death at somewhat 

 higher doses. It seems evident that at extremely high doses of radiation, 

 vessels, glia, and neurons all sufTer damage. There may be a level of radia- 

 tion, however, at which the neuronal damage is secondarily brought on by 

 damage to the functional integrity of the capillary system. 



Radiation Effects on Cerebral Vessels 



Doses of ionizing radiation to the brain which have been reported capable 

 of producing radiation lesions have, in virtually every instance, involved 

 not only nerve cells and fibers, but also the vascular system. The vascular 

 reaction to radiation in the brain is characterized by generalized vasculitis, 

 brain edema, and vascular fragility I Lyman ct al., 1933, 1952; DavidofT 

 et al, 1938; Russell et al, 1949; Colwcll and Gladstone, 1937; Haymaker 

 et al, 1958). Similar vascular reactions following irradiation have been 

 described in skin ( Wolback, 1909, 1925; MacKee, 1938; Miescher, 1930; 

 Snider, 1948), lung (Englestad, 1934; Warren and Spencer, 1940), and 

 kidney (Warren, 1936). 



Observations on the fate of capillaries in radiated skin and in developing 

 granulation tissue reveal that endothelial protoplasmic buds retract and be- 

 gin to become obliterated at about 400 r, even though inhibition of granula- 

 tion tissue does not occur until 2,000 r is administered. Under these circum- 

 stances there is swelling of the endothelium, producing first a narrowing of 

 the lumen and then a dilitation which results in a primary radiation ery- 

 thema. Edema ensues, apparently being dependent on the reactivity of the 

 capillary endothelium and of the surrounding parenchyma (Van den 

 Brenk, 1959; Borak, 1942a,b,c). Following the edema, diapedesis of cellular 

 elements through the vessel wall occurs, involving lymphocytes, red blood 

 cells, and polymorphonuclear leucocytes. This results in the commonly ob- 

 served inflammatory response of the perivascular tissue to radiation. 



One of the reported effects of ionizing radiation on cells is the intracellular 

 disintegration of large protein molecules into those of smaller size. This re- 

 sults in an increase in osmotic pressure leading to imbibition of fluid by the 

 cell (Heilbrunn and Mazia, 1936; Borak, 1942a). Endothelial cells in the 

 brain prove no exception. An increase in basophilia and endothelial cell 

 swelling were among the first reactions observed by Clemente et al ( 1959, 

 1960) in cerebral capillaries of neonatal rats subjected to 500 r doses of 



