Alcohol-mediated purkinje cell loss in the absence of hypoxemia during thethird trimester in an ovine model system

Background: Although the mechanisms that underlie fetal alcohol-induced neu ronal loss have not been determined, hypoxia/hypoxemia has been considered a leading candidate; This study was designed to test the hypothesis that ne uronal loss could occur in the developing brain in the absence of fetal hyp oxemia. Methods: Three groups of pregnant sheep were used: a control group, a binge -drinking group, and a pair-fed group. The alcohol and pair-fed animals wer e anesthetized on day 113 of pregnancy, and the mothers and fetuses were in strumented with arterial and venous catheters. All animals were killed on d ay 133. Stereological cell counting techniques were used to estimate the to tal number of Purkinje cells in the fetal cerebellum. Results: Peak maternal and fetal blood alcohol concentrations did not produ ce fetal hypoxemia. Nevertheless, there was a 25% loss of Purkinje cells of the cerebellum in the alcohol-exposed fetuses compared with that in the pa ir-fed controls. The loss of neurons was not accompanied by microencephaly or a concomitant decrease in either cerebellar weight or volume of the feta l cerebellum. Conclusions: Neuronal loss can be observed after alcohol exposure during th e third trimester equivalent in fetal sheep in the absence of alcohol-induc ed hypoxemia. Furthermore, cell loss in the absence of deficits in gross br ain weight or regional brain volume indicates that the lack of gross brain volume deficits from magnetic resonance imaging techniques is not a reliabl e indication that the brain is unaffected by the alcohol exposure.