Mechanisms of alcohol-induced neuroteratology: an examination of the roles of fetal cerebral blood flow and hypoxia

Abstract

Hypoxia (decreased tissue oxygen levels) has long been considered as a possible mechanism of alcohol-induced developmental deficits, yet research has not conclusively disproved this hypothesis, nor has it provided substantial evidence for a mechanism of developmental alcohol insults involving hypoxia. Previous research has shown that moderate acute doses of alcohol does not induce hypoxemia (decreased arterial oxygen levels), yet these same studies have shown that this same alcohol exposure does transiently decrease cerebral blood flow (CBF). This is significant because although developmental alcohol exposure did not result in hypoxemia, the decreases in CBF seen in these previous studies may induce hypoxia within the brain. Unfortunately, these experiments were only performed after acute doses of alcohol, so it is unknown if a more chronic or repeated alcohol exposure paradigm would have similar effects. The present study examined blood flow in the sheep fetus after repeated alcohol exposure in a bingelike paradigm throughout the third trimester. Additionally, this study examined the fetal neurovascular response to a subsequent infusion of alcohol after the repeated alcohol exposure. This latter experiment was designed to examine the hypothesis that alcohol exposure throughout the third trimester affects the normal responsiveness of the neurovasculature to alcohol (compared to previous research demonstrating acute alcohol-induced decreases in CBF). The results from the present experiments indicate that although few regions were significant, the majority of the regions (especially the brain regions) exhibited a trend for increases in blood flows after alcohol exposure. This phenomenon was especially prominent in the group receiving the lower dose of alcohol. Additionally, the data from this study demonstrated that after repeated alcohol exposures the near-term sheep fetus did not respond to a subsequent dose of alcohol in a similar manner seen in previous experiments when the acute alcohol exposure was administered in alcohol naïve animals. After the final alcohol exposure the subjects in this study had either no effect in terms of blood flow or an increase in CBF. This is opposite to previous observations which demonstrated reduced blood flow in numerous brain regions. The present experiments suggest that alcohol does not induce fetal hypoxia, but does negatively affect the normal neurovascular response to alcohol. This latter phenomenon could have negative consequences on future development of the brain.