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Prenatal cannabinoid exposure induces significant vasoconstriction in the fetal brain

20 Aug | By Biophotonics.World
Prenatal cannabinoid exposure induces significant vasoconstriction in the fetal brain
Figure 1 Maximum intensity projections of 3D cm-OCA images of the murine fetal brain vasculature (a) before and (b) 45 minutes after SCB exposure. Maximum intensity projections of 3D cm-OCA images of the murine fetal brain vasculature (c) before and (b) 45 minutes after vehicle exposure (the solvent without the SCB).

Recreational and medicinal marijuana use has increased over the past decade. Due to its legalization in several states across the United States, marijuana has become easily accessible and is a commonly abuse substance during pregnancy. Synthetic cannabinoids (SCBs) are a group of heterogeneous compounds that were developed to understand the endogenous cannabinoid system and as potential therapeutics. SCB’s popularity and use has drastically increased they produce similar psychoactive effects like natural cannabinoids, are easily available in ready-to-use formulations and are undetectable in routine drug screenings.

SCBs are 40- to 600-fold more potent than Δ9-tetrahydrocannbinol (Δ9-THC), the major psychoactive component of marijuana, but SCBs and Δ9-THC target similar receptors. Their extremely high potency combined with their higher binding affinities with cannabinoid receptors, make SCBs more toxic than Δ9-THC. Moreover, Δ9-THC, can cross the fetoplacental barrier and are secreted through breast milk. The increase in natural and SCB use combined with the prevalence of unplanned pregnancies, emphasize the need to study the effects of cannabinoids on embryonic development.

The second trimester is considered the peak period of fetal neurogenesis and angiogenesis, and endocannabinoid signaling plays a pivotal role in brain development. Thus, studying the changes in the embryonic brain development due to maternal cannabinoid exposure during the second trimester is of immense importance. To study cannabinoid exposure, we utilize a murine model due to its genetic and phenotypic developmental similarity to humans. However, imaging murine brain development is a challenge.

Optical coherence tomography (OCT) is a well-developed optical imaging modality with high spatial and temporal resolution. OCT was initially developed for ophthalmic imaging, has been used over the past decade to image small animal embryos due to its noninvasive nature and real-time cross-sectional imaging capability. In addition to traditional structural imaging, several functional extensions of OCT have been developed for specific imaging targets. One such extension, correlation mapping optical coherence angiography (cm-OCA), can be used to image the murine fetal brain microvasculature.

Researchers at the University of Houston and Texas AM University, lead by Prof. Larin, have recently used in uterocm-OCA to image changes in murine fetal brain vasculature due to maternal exposure to CP-55,940, a commonly used and well-characterized synthetic cannabinoid. Within 45 minutes of maternal SCB exposure, the team demonstrated that there was a substantial decrease in vessel area density, vessel length fraction, and vessel diameter as compared to the sham group. These changes significantly reduce nutrients delivery to the developing brain, and, potentially, harmful for overall embryonic development. 

These studies are the first step to understand the effect of marijuana on the pregnancy. The emerging practice of cannabinoid use among young adults of child-bearing age makes it imperitive to investigate the additional risk for adverse infant outcomes due to such prenatal use. 

Author: Kirill Larin

Original article: https://onlinelibrary.wiley.com/doi/full/10.1002/jbio.201900050


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