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.
One of the most common reasons of congenital birth defects is prenatal substance abuse. The severity of the defect depends on the amount of substance abused and the period of gestation during which substance is abused. Although prenatal substance abuse is common during the first trimester, some women continue the abuse well into their second trimester, which is considered the peak period for fetal neurogenesis and angiogenesis. Thus, evaluating the changes in fetal brain vasculature caused by maternal exposure to different teratogens at the second trimester equivalent period is crucial. In this study we use correlation mapping optical coherence angiography (cm-OCA), a functional extension of optical coherence tomography, to image changes in murine fetal brain vasculature caused due to prenatal exposure to ethanol, cannabinoids, or nicotine. Results showed significant vasoconstriction in all three cases.
In the United States, 20% of pregnant women are estimated to smoke, thus affecting 800,000 babies annually. Maternal nicotine exposure is known to have several detrimental effects on the developing fetus including intrauterine growth restriction, perinatal mortality and morbidity, placental abruption, and other childhood disorders. In humans, studies evaluating the association between maternal cigarette smoking during pregnancy and behavioral development in offsprings have shown negative influences of nicotine on brain development. Although several studies have documented lower birth weights, morphological and behavioral changes, not much has been done evaluating the acute changes in brain vasculature after prenatal exposure to nicotine. This work uses correlation mapping optical coherence angiography (cm-OCA), a functional extension of optical coherence tomography, to evaluate changes in murine fetal brain vasculature, in utero, minutes after maternal nicotine exposure. A rapid and significant decrease in vasculature was observed compared to the sham group.
Prenatal substance abuse is one of the main causes of birth defects. Depending upon the substance being abused and the period of gestation during which the abuse happens, the severity of the defect is determined. Although prenatal substance abuse during the first trimester is common, the prevalence of unplanned pregnancies in the United States have led to women continuing their substance abuse well into the second trimester. The second trimester is the peak period for fetal neurogenesis and angiogenesis. Hence, any exposure to teratogens during this period is known to hinder brain development. Several studies have documented changes in morphology and behavior due to exposure to teratogens during this period. However, not a lot is known about the changes in vasculature in the developing brain. In this study, we used angiographic optical coherence tomography, a functional extension of optical coherence tomography, to image acute vasculature changes in the fetal brain caused due to prenatal exposure to ethanol, nicotine, and synthetic cannabinoids (SCB). Results showed a significant decrease in vasculature in all three cases compared to their respective sham groups.
Prenatal substance abuse is a major public health concern. Much research has been focused on alcohol and other drug use, but there is a lack of information about prenatal cannabinoid use. Nevertheless, marijuana use during pregnancy increases the risk of a stillbirth by approximately 2.3X. Synthetic cannabinoids (SCB) are a group of heterogeneous compounds which were developed to understand the endogenous cannabinoid system and as potential therapeutics. SCBs are legally available for purchase in several places, and the use of natural and synthetic cannabinoids is high among women of reproductive age. Combined with the prevalence of unplanned pregnancies, the high use of cannabinoids may lead to an increase in prenatal exposure to cannabinoids. Early studies have shown morphological and behavioral anomalies similar to fetal alcohol syndrome. Even though the mechanisms of Δ9 -tetrahydrocannabinol (Δ9 -THC), the major psychoactive component of marijuana, and SCB are similar, there are several important differences. Subsequently, some SCBs have a 40 to 600 fold higher potency than Δ9 -THC. However, there is paucity of research focused on the prenatal effects of SCBs. This study uses correlation mapping optical coherence tomography (cm-OCT) to evaluate acute changes in the murine fetal brain vasculature in utero after exposure to CP-55,940, a well-characterized and commonly used reference compound in cannabinoid research. Our results showed a rapid decrease in parameters quantifying vasculature, i.e., vessel area density, and vessel length fraction, as compared to the sham group, demonstrating a dramatic and rapid effect of cannabinoids on fetal brain vasculature. Our work shows the need for further research on the effects of cannabinoids on fetal development.
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