Development of resistance to lead encephalopathy during maturation in the rat pup

The purpose of this study was to determine the maturational period during which the rat pup becomes resistant to the toxic effects of lead on the brain. Pups were fed lead, as lead acetate, by esophageal catheter for 14 days beginning at various ages between 14-24 days. The daily lead doses, which produced a hemorrhagic cerebellar encephalopathy in at least 50% of pups, were 400 micrograms Pb/g body weight for animals fed from 14 days of age, 800 micrograms/g for animals fed from 16 days, and 1600 micrograms/g for animals fed from 18 days. In contrast, pups fed even higher lead doses beginning at 20 days showed only a patchy cerebellar edema by light microscopy while pups fed from 24 days had normal cerebellums by light microscopy. The encephalopathic lead doses in the younger pups resulted in the same cerebellar lead concentrations (about 30 micrograms/g protein) as the higher lead doses fed pups beginning at 20 ot 24 days. When corrected for blood lead concentrations, the cerebellar lead concentrations were 20-25% higher in the encephalopathic compared to the older encephalopathy-resistant animals. This difference may be accounted for by cerebellar hemorrhages in the younger animals. Polarographic studies showed inhibition of respiration in cerebellar slices from animals fed lead from 14 days of age but not in animals fed from 20 or 24 days of age. Our results that, during the encephalopathy-sensitive age period, a critical cerebellar concentration of lead is associated with the encephalopathy. Resistance to lead encephalopathy in older animals, with similar cerebellar lead concentrations, may be related to a capacity to sequester lead in new cellular locations away from its site of action on aerobic energy metabolism.