The pathogenesis of hydrocephalus in newborn rats deficient in vitamin B12.

Richardson & Hogan (1946) produced hydrocephalus in rats by feeding a purified casein diet containing all the vitamins available at that time. Almost 2 % of the young from females fed the experimental diet were hydrocephalic; female rats fed the same diet supplemented with liver extract gave birth to normal young. It is now thought that this diet was marginally deficient in vitamin B12 (Newberne & O'Dell, 1961). Animals which showed no gross evidence of lesions in the central nervous system had reduced maze-learning abilities as compared to animals on control diets (Whitley, O'Dell & Hogan, 1951). The frequency in occurrence of hydrocephalus was greatly increased by changing the source of protein in the diet from casein to soybean oil meal, and also by adding X-methyl folic acid. Vegetable proteins, such as soybean oil meal, are known to have a lower content of vitamin B12 than does the protein from milk. The use of the folic acid antagonist produced spina bifida, cranium bifida, anophthalmia, microphthaknia, cleft palate, short mandible, and edema in addition to hydrocephalus (O'Dell, Whitley & Hogan, 1951). The addition of vitamin B12 to the antagonist-containing diet prevented the occurrence of hydrocephalus. Hydrocephalus in offspring littered to vitamin B12-depleted dams was not prevented by the addition of folic acid to the ration. Giroud, Lefebvres & Dupuis (1952) used 5 % succinylsulfathiazole in a purified diet to produce a folic-acid deficiency in mother rats, and hydrocephalus was observed in many of the young from these females. O'Dell, Whitley & Hogan (1948) were also able to show that if female rats are depleted of vitamin B12 they produce litters with a high incidence of hydrocephalus. This was true even though the diet was supplemented with folic acid and did not contain a folic acid antagonist. The parenteral administration of