Prenatal Binge-Like Alcohol Exposure in the Rat Results in Region-Specific Deficits in Brain Growth

Abstract

Children of women who abuse alcohol during pregnancy may be affected by varying degrees of neurological abnormality, even if they are not diagnosed with Fetal Alcohol Syndrome. The extent of the behavioral deficits of the affected offspring may be a function of several factors, such as the differential vulnerability of the various regions of the brain-to-alcohol insult. In this study, groups of timed-pregnant rats were exposed to different doses of alcohol (EtOH 2.25, EtOH 4.5, EtOH 6.5 g/kg/day) or control conditions (maltose dextrin solution or no treatment) from embryonic day 1 (E1: sperm positive) to E20. On E33 (usually postnatal day 10), all pups were perfused. Their brains were removed, dissected into forebrain, cerebellum, and brainstem, and weighed. Blood alcohol concentrations (BACs) were measured on 4 different days of gestation, but the peak BACs across gestation for the three alcohol-treated groups averaged 142, 294, and 413 mg/dl for the EtOH 2.25, EtOH 4.5, and EtOH 6.5 g/kg groups, respectively. Analysis of the body weight data indicated that pups in the EtOH 6.5 g/kg group had a greater somatic growth deficit than pups from all other groups. Although the whole brain, forebrain, cerebellum, and brainstem weights of pups in the EtOH 6.5 g/kg group were significantly smaller than those in the control groups, within-treatment group analyses indicated that the cerebella of pups in the EtOH 6.5 g/kg group were more severely affected than were their forebrains or brainstems. The analyses of the brain region to body weight ratios revealed again that the cerebellum-to-body-weight ratio of pups in the EtOH 6.5 g/kg group was more severely affected than the forebrain or brainstem to body weight ratios. Collectively, these data lend support to the view that gross regions of the brain are differentially vulnerable to alcohol insult during the first two trimesters equivalent, and suggest that the cerebellum is vulnerable to injury from exposure to high BACs during a developmental period other than the third trimester equivalent.