Document Detail


The effects of binge alcohol exposure in the 2nd trimester on the estimated density of cerebral microvessels in near-term fetal sheep.
MedLine Citation:
PMID:  18657528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 mm(3), 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.
Authors:
Katherine E Simon; Robin L Mondares; Donald E Born; Christine A Gleason
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-15
Journal Detail:
Title:  Brain research     Volume:  1231     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-08     Completed Date:  2009-01-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  75-80     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Washington, Seattle, WA, USA.
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MeSH Terms
Descriptor/Qualifier:
Alcohol-Induced Disorders, Nervous System / pathology*,  physiopathology
Alcoholism / complications
Animals
Arterioles / abnormalities,  drug effects,  physiopathology
Central Nervous System Depressants / toxicity
Cerebral Arteries / abnormalities*,  drug effects*,  physiopathology
Cerebrovascular Circulation / drug effects
Disease Models, Animal
Ethanol / toxicity
Female
Fetal Alcohol Syndrome / pathology*,  physiopathology
Hypoxia, Brain / physiopathology
Male
Microcirculation / drug effects*
Neovascularization, Physiologic / drug effects
Nitric Oxide Synthase Type III / drug effects,  metabolism
Organ Size / drug effects
Pregnancy
Pregnancy Trimester, Second / drug effects
Prosencephalon / blood supply,  drug effects,  physiopathology
Sheep
Grant Support
ID/Acronym/Agency:
R01 AA 12403/AA/NIAAA NIH HHS; R01 AA012403-01/AA/NIAAA NIH HHS; R01 AA012403-02/AA/NIAAA NIH HHS; R01 AA012403-02S1/AA/NIAAA NIH HHS; R01 AA012403-03/AA/NIAAA NIH HHS; R01 AA012403-04/AA/NIAAA NIH HHS; R01 AA012403-05/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Central Nervous System Depressants; 64-17-5/Ethanol; EC 1.14.13.39/Nitric Oxide Synthase Type III
Comments/Corrections

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