Dose-response analysis of microvasculature changes in the murine fetal brain and the maternal extremities due to prenatal ethanol exposure

Abstract

Significance: Prenatal exposure to ethanol causes several morphological and neurobehavioral deficits. While there are some studies on the effects of ethanol exposure on blood flow, research focusing on acute changes in the microvasculature is limited. Aim: The first aim of this study was to assess the dose-dependent changes in murine fetal brain microvasculature of developing fetuses in response to maternal alcohol consumption. The second aim was to quantify changes in vasculature occurring concurrently in the mother's hindlimb and the fetus's brain after maternal exposure to alcohol. Approach: Correlation mapping optical coherence angiography was used to evaluate the effects of prenatal exposure to different doses of ethanol (3, 1.5, and 0.75 g∕kg) on murine fetal brain vasculature in utero. Additionally, simultaneous imaging of maternal peripheral vessels and the fetal brain vasculature was performed to assess changes of the vasculature occurring concurrently in response to ethanol consumption. Results: The fetal brain vessel diameters (VDs) decreased by ∼47%, 30%, and 14% in response to ethanol doses of 3, 1.5, and 0.75 g∕kg, respectively. However, the mother's hindlimb VD increased by 63% in response to ethanol at a dose of 3 g∕kg. Conclusions: Results showed a dose-dependent reduction in vascular blood flow in fetal brain vessels when the mother was exposed to ethanol, whereas vessels in the maternal hindlimb exhibited concurrent vasodilation.

Brain Iron and Mental Health Symptoms in Youth with and without Prenatal Alcohol Exposure

“…Increased ferritin iron stores may reflect sufficient brain iron available for use, stored iron that is unavailable, or an overload of brain iron. Raghunathan and colleagues [ 72 ] propose that PAE alters brain vasculature, resulting in decreased brain vessel diameter, which may decrease heme iron. However, heme iron is not expected to contribute significantly to susceptibility [ 73 ] in subcortical brain structures.…”

Phenotype and synthesis activity of joint chondrocytes extracted from newborn rats with prenatal ethanol exposure

“…The present study demonstrates that ethanol consumption during pregnancy alters the phenotype and activity of offspring chondrocytes, characterized by higher AP activity, cellularity, and collagen type II expression, and lower SOX-9 expression, which may be mechanisms by which endochondral bone formation is compromised by maternal ethanol consumption. The effects of ethanol are considered dose-dependent [23][24][25] ; that is, they can vary according to the volume consumed daily, with consumption classified as discrete, moderate, or intense. 26 In the present study, rats in the ethanol group received a daily dose that would correspond to approximately 15-30 g of ethanol per day in humans, classified as moderate-to-intense consumption.…”

Optical coherence angiography to assess the dose-effect relationship of prenatal alcohol exposure on fetal brain vasculature

“…Mice were checked for vaginal plugs the morning after mating was set up, and once found, it was considered GD 0. dosed with 1.5 g/kg, 3.0 g/kg, and 4.5 g/kg of ethanol (95% w/v) via intragastric gavage at GD 12.5 (N=5), 13.5 (N=5), and 14.5 (N=5), which was followed by imaging at GD 14.5 to analyze if there was a multiple dose-dependent effect on the fetal brain vascular flow seen in our previous work. 4,9 To assess the acute effects of prenatal alcohol exposure on the fetal brain vasculature, the mice were dosed with 1.5 g/kg (N=2) 3.0 g/kg (N=2), and 4.5 g/kg (N=2) of ethanol (95% w/v) via intragastric gavage at GD 14.5 and imaged immediately following ethanol exposure. Sham exposures were performed with administration of distilled water for each of the sets of experiments N=3 repeat exposure, N=2 for acute exposure.…”