The effects of binge alcohol exposure in the 2nd trimester on the estimated density of cerebral microvessels in near-term fetal sheep

• Published in: Brain research Vol. 1231; pp. 75 - 80
• Main Authors: Simon, Katherine E, Mondares, Robin L, Born, Donald E, Gleason, Christine A
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 22.09.2008; Amsterdam Elsevier; New York, NY
• Subjects: Alcohol-Induced Disorders, Nervous System - pathology; Alcohol-Induced Disorders, Nervous System - physiopathology; Alcoholism - complications; Alcoholism and acute alcohol poisoning; Animals; Arterioles - abnormalities; Arterioles - drug effects; Arterioles - physiopathology; Biological and medical sciences; Central Nervous System Depressants - toxicity; Cerebral Arteries - abnormalities; Cerebral Arteries - drug effects; Cerebral Arteries - physiopathology; Cerebral microvessel density; Cerebrovascular Circulation - drug effects; Disease Models, Animal; Ethanol - toxicity; Female; Fetal Alcohol Spectrum Disorders - pathology; Fetal Alcohol Spectrum Disorders - physiopathology; Fetal alcohol syndrome; Hypoxia, Brain - physiopathology; Male; Medical sciences; Microcirculation - drug effects; Neovascularization, Physiologic - drug effects; Neurology; Nitric Oxide Synthase Type III - drug effects; Nitric Oxide Synthase Type III - metabolism; Organ Size - drug effects; Pregnancy; Pregnancy Trimester, Second - drug effects; Prosencephalon - blood supply; Prosencephalon - drug effects; Prosencephalon - physiopathology; Sheep; Toxicology; Fetal alcohol syndrome; Sheep; Cerebral microvessel density; Ethanol; Central nervous system; Alcohol; Density; Encephalon; Alcoholic beverage; Microcirculation; Newborn diseases; Vertebrata; Mammalia; Animal; Fetus; Artiodactyla; Ungulata
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.06.125

Abstract Heavy fetal alcohol exposure is associated with a spectrum of neurological abnormalities, although the mechanism of injury is largely unknown. We previously reported attenuated cerebral blood flow response to hypoxia in fetal and newborn sheep which were exposed to alcohol earlier in pregnancy. One possible mechanism for this effect of alcohol on the developing cerebral vasculature is a decrease in cerebral microvessel density, similar to its effect on developing neurons. Therefore, we tested the hypothesis that prenatal alcohol exposure decreases cerebral microvessel density. Pregnant ewes received intravenous infusions of ethanol or saline during days 60–84 of gestation (term = 150 days) and at 125 days of gestation we obtained the fetal brains for study. We immunohistochemically labeled vessels of the left cerebral forebrain hemispheres with antibody to endothelial nitric oxide synthase and then obtained unbiased stereological estimates of cerebral microvessel density using a modified optical fractionator method. We studied 20 fetal brains of which 9 were alcohol-exposed, 11 were saline-controls, and all were products of a twin gestation. Although brain and body weights were not different between groups, the alcohol-exposed group had significantly lower brain weight as a percentage of body weight. Estimates of cerebral microvessel density were not significantly different between alcohol-exposed and saline-control groups: 12.7 ± 8.7 and 9.1 ± 2.8 microvessels per mm3 , respectively (mean ± SD, p = 0.32). Since there is no change in estimated cerebral microvessel density after prenatal alcohol exposure, we conclude that decreased cerebral microvessel density is not a likely explanation for attenuated cerebral blood flow in response to hypoxia.