Maternal binge drinking and fetal neuronal damage
Article first published online: 31 JUL 2007
© 2007 The Author. Journal compilation © 2007 The Physiological Society
Volume 92, Issue 5, page 821, September 2007
How to Cite
Wood, C. E. (2007), Maternal binge drinking and fetal neuronal damage. Experimental Physiology, 92: 821. doi: 10.1113/expphysiol.2007.038448
- Issue published online: 17 AUG 2007
- Article first published online: 31 JUL 2007
- (Received 12 June 2007; accepted after revision 20 June 2007; first published online 30 July 2007)
Maternal binge drinking has obvious detrimental effects on the developing fetus. These effects include development of the phenotype of the fetal alcohol spectrum disorder and disordered development of the central nervous system (CNS). The mechanism of the CNS damage has been speculated to be fetal hypoxia or, perhaps more pertinently, fetal CNS tissue hypoxia. This hypothesis is not easily examined in small animal models of fetal alcohol exposure because of the inaccessibility of the developing fetus in utero. The report by Parnell et al. (2007) in this issue of Experimental Physiology directly addresses this important question using the fetal sheep, a well-established model of fetal development that has long been used to unravel the mysteries of fetal cardiovascular function and regulation in utero. This team of investigators has developed a ‘binge drinking’ regimen in which chronically catheterized pregnant sheep were infused with ethanol at two different doses, raising plasma ethanol concentrations to levels observed in human binge drinkers. The sheep were subjected to ‘binge drinking’ from 109 to 132 days gestation (the length of pregnancy in the sheep is 147 days). Fetal cardiovascular and blood gas responses to the ethanol were measured in response to the final bolus treatment with ethanol.
Contrary to a widely held assumption, the ‘binge drinking’ regimen did not result in reductions in cerebral blood flow. Surprisingly, the higher dose of alcohol increased regional fetal cerebral blood flow and increased oxygen delivery to the fetal brain. Despite the increase in oxygen delivery to the cerebellum, these fetuses demonstrated a reduction in Purkinje cell density in the cerebellum, a hallmark consequence of alcohol exposure in fetuses. What, therefore, accounts for the neuronal damage in response to alcohol exposure? As suggested in a recent study by Maycock et al. (2007), the vasodilatory response of the cerebral vasculature to fetal hypoxia is limited; perhaps this reduction in the reserve of the fetus to increase cerebral blood flow during hypoxic episodes might result in neuronal damage and neurodevelopmental disturbances. In contrast, the mediator of damage might be more direct.
In the present study by Parnell et al. (2007), there is a clear acidaemia and hypercapnia in response to ethanol exposure. Binge drinking produces repeated bouts of hypercapnia and acidaemia that are not normally found in the undisturbed fetus in utero. Fetal cardiovascular reflexes aggressively defend blood gas and pH homeostasis in late gestation (Itskovitz et al. 1991; Raff et al. 1992; Giussani et al. 1993). A most interesting question arising from this work is whether the repeated changes in fetal blood gas status are directly neurotoxic or, perhaps, are indirectly neurotoxic via stimulation of local mediators of programmed cell death. The use of the fetal sheep model to answer these questions can be an important experimental tool that allows direct monitoring and manipulation of physiological variables in the fetus.
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