Prenatal alcohol exposure is a well-known cause of preventable birth defects, resulting in a decrease in cerebrovascular blood flow, which may cause major neurodevelopmental and morphological alterations in the developing fetus. In this study, we assess the acute and persistent effects of alcohol exposure on fetal brain vasculature in utero. We also analyzed the effects of different alcohol dosages (1.5 g/kg, 3.0 g/kg, and 4.5 g/kg) on fetal brain vasculature. To assess the effects of persistent alcohol exposure, we administered the same dose of alcohol at multiple gestational days (GD12.5, 13.5, and 14.5). To assess the acute effects, we administered the alcohol only at GD14.5. We utilize correlation mapping optical coherence angiography to image changes in fetal brain vasculature caused by exposure to ethanol at each dosage. Results show significant vasoconstriction of the main blood vessel imaged, which is located at the terminal anterior and middle cerebral arteries, irrigating the dorsolateral surface of the embryonic brain, for all three administered dosages. The difference in the primary blood vessel diameter before and after the final ethanol exposure at GD14.5 shows that the greater the dose, the smaller the change in blood vessel diameter. This contrasts with the acute dosing effects, which show a greater change in the primary blood vessel diameter when administering the highest single ethanol dosage. Overall, the multiple dosing and acute effects of alcohol consumption demonstrated a decrease in blood flow in the fetal brain.
SignificanceMaternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development.AimWe use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine.ApproachEthanol (16.6% v/v, at a dose of 0.75g / kg) and nicotine (at a dose of 0.1 mg / kg) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45 min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: 0.75 g / kg) or nicotine (dose: 0.1 mg / kg).ResultsWhile results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure.ConclusionResults suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.
Systemic Sclerosis (SSc) is a chronic disease of autoimmune etiology that causes vasomotor disturbance, fibrosis, and atrophy of skin, underlying tissue, muscles, and internal organs. It manifests in about 30 people per million every year, and there are an estimated three million cases worldwide. Currently, SSc is assessed using the modified Rodnan Skin Score (mRSS), which is a manual palpation test on 17 sites that requires extensive physician training and experience for accurate assessments. Unfortunately, mRSS has very high inter-observer variability and is subjective. Optical coherence elastography (OCE) is a well-established technique for assessing the mechanical properties of tissues with sub-millimeter spatial resolution. In this work, OCE was used to non-invasively assess the mechanical properties of mouse skin in vivo. OCE measurements were performed on 3 groups of mice, (1) control group that was injected with PBS, (2) SSc group that was injected with bleomycin (BLM) to induce SSc, and (3) treatment group that was first injected with BLM and then injected with imatinib, which is postulated to reduce disease in SSc. The wave speed in BLM-SSc skin was significantly higher than that of normal skin (p<0.05). The wave speed in murine skin in the treatment group was slightly lower as compared to the BLM-SSc skin, but the difference was not significant. These results demonstrate the ability of OCE to monitor SSc disease and treatment response and support further evaluation of this platform in monitoring SSc in the clinic.
The heart is the first essential organ that develops during organogenesis. Fetal impaired heart function correlates to functional cardiac anomalies and heart defects in adulthood. Therefore, noninvasive assessment of dynamic functional cardiac events during pregnancy is essential for early diagnosis of cardiac diseases. However, visualization and analysis of the small yet fast-beating embryonic heart require a high-resolution imaging platform to provide reliable volumetric analyses. Optoacoustic (OA) imaging provides excellent optical contrast along with high spatial resolution and has demonstrated an exclusive potential for noninvasive deep-tissue visualization. In this study, we used volumetric OA imaging to visualize the embryonic heart at gestational day (GD) 16.5. The anatomical structure of the embryonic heart and cardiac vasculature was visualized in three orthogonal imaging planes allowing for further quantification and structural measurements. Twenty-five volumes per second temporal resolution of OA imaging enabled assessment of embryonic cardiac dynamics. Using the temporal profile of the time-lapse OA data at different locations of the embryonic heart, the average heart rate of embryos was calculated. This study demonstrated the capability of volumetric OA tomography for noninvasive visualization of the embryonic heart and assessment of cardio dynamics at nearly video rate.
Prenatal alcohol exposure (PAE) is a leading cause of developmental disabilities worldwide and thus, is one of the best-known causes of preventable birth defects. Its effects can persist throughout life as physical and cognitive growth and development deficits. Previous studies have demonstrated that the acute effects of prenatal alcohol exposure on fetal brain vasculature diminish brain growth and decrease cerebrovascular blood flow. In this study, we use correlation mapping optical coherence angiography to assess the dose-effect relationship of prenatal alcohol exposure on fetal brain vasculature in utero in a mouse model (C57BL/6J). We evaluated multiple alcohol dosages (1.5 g/kg, 3.0 g/kg, and 4.5 g/kg) at gestational day (GD) 14.5 followed immediately by imaging at GD 14.5. We also studied multiple dosing effects by administering ethanol via intragastric gavage at GD 12.5, 13.5, and 14.5 for each dose (1.5 g/kg, 3.0 g/kg, and 4.5 g/kg) followed by imaging at GD 14.5. Results show vasoconstriction of the main imaged blood vessel after dosing for three consecutive days. When the embryo was exposed to the lowest dose, 1.5 g/kg of ethanol, there was a greater decrease in the main blood vessel diameter, compared to the highest dose, 4.5 g/kg of ethanol. For the acute dosing studies, where a single ethanol dose was administered at GD 14.5, the results show a higher percentage change in vessel diameter over time for 4.5 g/kg, which was the highest dose, but with a higher initial percentage change at a lower dose. The multiple dose and single dose exposure to ethanol results demonstrated significant changes in fetal brain vasculature. Multiple dosing of prenatal alcohol exposure shows a significant effect in the vasculature for each dosage, demonstrating the dose-effect relationship of multiple ethanol exposure on embryo brain vasculature compared to a single dose exposure.
Prenatal substance abuse is a leading cause of congenital defects. The severity of the defect caused depends on the substance used and the period of gestation during which the abuse happened. Several studies have documented the effects of alcohol and nicotine, used individually. However, the co-abuse of alcohol and nicotine is very common. There is not much literature on this. While first trimester substance abuse is common, several women continue to abuse substances well into their second trimester of pregnancy. The second trimester marks the peak period for fetal neurogenesis and angiogenesis. Exposure to any teratogen during this period is known to affect fetal brain development. This study uses optical coherence angiography to evaluate changes in fetal brain vasculature due to prenatal exposure to a combination of alcohol and nicotine. These results were compared to results from two other groups that were administered alcohol and nicotine independently. These comparisons showed a statistically significant difference between the nicotine group and the group that was administered both alcohol and nicotine, which was not seen with the alcohol group.
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