Neuronal deficits after neonatal exposure to phenobarbital

Heterogeneous Sabra mice pups were injected daily with 50 mg/kg (B50) phenobarbital or 40 mg/kg (B40) from age 2 to 21 days. Control litter mates (C) received vehicle injection. Brain phenobarbital concentrations attained 50 μg/g. The brains of C, B40, and B50 mice were removed at age 50 days, fixed, sectioned, and stained with hematoxylin and eosin. Matching sagittal sections were selected for the study of the cerebellum, hippocampus, and the cerebral cortex. Brain weight was reduced 8 to 12% compared with control among the phenobarbital-treated animals. There were reductions of about 20% in the area of the cerebellar layers in B50-treated mice but no significant differences in B40-treated mice. In both groups Purkinje and granule cell numbers were reduced by about one-third, the packing density of the cerebellar cells was also reduced (18% to 20%), and the area of the hippocampal layers was reduced by about 15 to 20%. There were one-third fewer pyramidal cells in B50- and B40-treated mice than in controls and 22 to 25% fewer granule cells. Therefore, the ratio granule:pyramidal cells was significantly different in the hippocampus. The cortical area was smaller than control in the B50 group (14%) and the B40 group (20%). The neuronal deficits in the cortex were less extensive than in the other brain parts studied (B50, 9%; B40, 19%). The resuls suggest that unlike many neonatal insults including undernutrition, neonatal administration of relatively small doses of phenobarbital destroys even brain cells which are already formed.