title: Binge alcohol exposure in the second trimester attenuates fetal cerebral blood flow response to hypoxia.
abstract: Alcohol is detrimental to the developing brain and remains the leading cause of mental retardation in developed countries. The mechanism of alcohol brain damage remains elusive. Studies of neurological problems in adults have focused on alcohol's cerebrovascular effects, because alcoholism is a major risk factor for stroke and cerebrovascular injuries. However, few studies have examined similar cerebrovascular effects of fetal alcohol exposure. We examined the effect of chronic binge alcohol exposure during the second trimester on fetal cerebrovascular and metabolic responses to hypoxia in near-term sheep and tested the hypothesis that fetal alcohol exposure would attenuate cerebrovascular dilation to hypoxia. Pregnant ewes were infused with alcohol (1.5 g/kg) or saline intravenously at 60-90 days of gestation (full term = 150 days). At 125 days of gestation, we measured fetal cerebral blood flow (CBF) and oxygen metabolism at baseline and during hypoxia. Maternal blood alcohol averaged 214 +/- 5.9 mg/dl immediately after the 1.5-h infusion, with similar values throughout the month of infusion. Hypoxia resulted in a robust increase in CBF in saline-infused fetuses. However, the CBF response to hypoxia in fetuses chronically exposed to alcohol was significantly attenuated. Cerebral oxygen delivery decreased in both groups of fetuses during hypoxia but to a greater degree in the alcohol-exposed fetuses. Prenatal alcohol exposure during the second trimester attenuates cerebrovascular responses to hypoxia in the third trimester. Altered cerebrovascular reactivity might be one mechanism for alcohol-related brain damage and might set the stage for further brain injury if a hypoxic insult occurs.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195-6320, USA. mayock@u.washington.edu
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Mayock
authors.forename: Dana
authors.initials: D
authors.lastname: Ness
authors.forename: Robin L
authors.initials: RL
authors.lastname: Mondares
authors.forename: Christine A
authors.initials: CA
authors.lastname: Gleason
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000431:Ethanol / Q000506:poisoning*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D005333:Fetus / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D012756:Sheep
chemical_list: D000431:Ethanol