Impact of maternal dietary folic acid or choline dietary deficiencies on vascular function in young and middle-aged female mouse offspring after ischemic stroke.

Adequate maternal dietary levels of one-carbon metabolites, such as folic acid and choline, play an important role in the closure of the neural tube in utero; however, the impact of deficiencies in one-carbon (1C) metabolism on offspring neurological function after birth remain undefined. Stroke is one of the leading causes of death and disability globally. The aim of our study was to determine the impact of maternal 1C nutritional deficiencies on cerebral and peripheral blood flow after ischemic stroke in adult female offspring. In this study, female mice were placed on either control (CD)-, folic acid (FADD)-, or choline (ChDD)-deficient diets before pregnancy. Female offspring were weaned onto a CD for the duration of the study. Ischemic stroke was induced in offspring and after 6 wk cerebral and peripheral blood flow velocity was measured using ultrasound imaging. Our data showed that 11.5-mo-old female offspring from ChDD mothers had reduced blood flow in the posterior cerebral artery compared with controls. In peripheral blood flow velocity measurements, we report an aging effect. These results emphasize the importance of maternal 1C diet in early life neuro-programming on long-term vasculature health.NEW & NOTEWORTHY We demonstrate that a maternal dietary deficiency in one-carbon (1C) metabolites result in reduced cerebral blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuroprogramming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.

Measurement of Endothelium-dependent Vasorelaxation in the Mouse Thoracic Aorta using Tensometric Small Volume Chamber Myography.

Small volume chamber tensometric myography is a commonly used technique to evaluate the vascular contractility of small and large blood vessels in laboratory animals and small arteries isolated from human tissue. The technique allows researchers to maintain isolated blood vessels in a tightly controlled and standardized (near-physiological) setting, with the option of adjusting to various environmental factors, while challenging the isolated vessels with different pharmacological agents that can induce vasoconstriction or vasodilation. The myograph chamber also provides a platform to measure vascular reactivity in response to various hormones, inhibitors, and agonists that may impact the function of smooth muscle and endothelial layers separately or simultaneously. The blood vessel wall is a complex structure consisting of three different layers: the intima (endothelial layer), media (smooth muscle and elastin fibers), and adventitia (collagen and other connective tissue). To gain a clear understanding of the functional properties of each layer, it is critical to have access to an experimental platform and system that would allow for a combinational approach to study all three layers simultaneously. Such an approach demands access to a semi-physiological condition that would mimic the in vivo environment in an ex vivo setting. Small volume chamber tensometric myography has provided an ideal environment to evaluate the impact of environmental cues, experimental variables, or pharmacological agonists and antagonists on vascular properties. For many years, scientists have used the tensometric myograph technique to measure endothelial function and smooth muscle contractility in response to different agents. In this report, a small volume chamber tensometric myograph system is used to measure endothelial function in the isolated mouse aorta. This report focuses on how small volume chamber tensometric myography can be used to evaluate the functional integrity of the endothelium in small segments of a large artery such as the thoracic aorta.

Can 10 000 Healthy Steps a Day Slow Aortic Root Dilation in Pediatric Patients With Marfan Syndrome?

Background Stiffer aortas are associated with a faster rate of aortic root (AoR) dilation and higher risk of aortic dissection in patients with Marfan syndrome. We have previously shown that mild aerobic exercise reduces aortic stiffness and rate of AoR dilation in a Marfan mouse model. In this study, we investigated if these results could be translated to pediatric patients with Marfan syndrome. Methods and Results We enrolled 24 patients with Marfan syndrome aged 8 to 19 years to participate in a 6-month physical activity intervention, excluding those with ventricular dysfunction or prior history of aortic surgery. We instructed patients to take 10 000 steps per day, tracked by an activity tracker. At baseline and 6 months, we measured AoR dimension, arterial stiffness, endothelial function, physical activity indices, inflammatory biomarkers, and coping scores. Controls consisted of 15 age-matched patients with Marfan syndrome. Twenty-four patients with Marfan syndrome (median age, 14.4 years [interquartile range {IQR}, 12.2-16.8], 14 male patients) were enrolled. Baseline assessment demonstrated that the majority of these patients were sedentary and had abnormal arterial health. Twenty-two patients completed the intervention and took an average of 7709±2177 steps per day (median, 7627 [IQR, 6344-9671]). Patients wore their Garmin trackers at a median of 92.8% (IQR, 84%-97%) of their intervention days. AoR Z score in the intervention group had a significantly lower rate of change per year compared with the controls (rate of change, -0.24 versus +0.008; P=0.01). Conclusions In this clinical intervention in pediatric patients with Marfan syndrome, we demonstrated that a simple physical activity intervention was feasible in this population and has the potential to decrease the AoR dilation rate. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03567460.

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors.

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires spatiotemporally precise measurement of neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in mouse striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in mouse cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.

Comparison of two different direct digital radiography systems for the ability to detect artificially prepared periapical lesions.

The purpose of this study was to compare Schick CDR and Trophy RVGui direct digital radiography (DDR) systems for the ability to detect periapical lesions in human cadaver mandibles. Digital radiographs were exposed of teeth with normal periapical areas and of teeth with artificially prepared periapical lesions using both DDR systems. Three examiners independently viewed the images at two different time periods and estimated which bony state was present. The resulting data were subjected to statistical analysis using a two-way ANOVA. Interexaminer variability was statistically analyzed using Spearman's rho. There was no significant difference in the level of accuracy between the two different DDR systems at either observation period. There was a statistically significant high level of agreement between examiners (p < 0.01). In conclusion, there was no significant difference in the accuracy of detecting artificially prepared periapical lesions between Schick CDR and Trophy RVGui DDR systems.

Evidence of nanobacterial-like structures in calcified human arteries and cardiac valves.

Mechanisms mediating vascular calcification remain incompletely understood. Nanometer scale objects hypothesized to be a type of bacteria (nanobacteria) are associated with calcified geological specimens, human kidney stones, and psammona bodies in ovarian cancer. Experiments were designed to evaluate human vascular tissue for the presence of similar nanometer-scale objects. Calcified human aneurysms (n = 8), carotid plaques (n = 2), femoral arterial plaques (n = 2), and cardiac valves (n = 2) and noncalcified aneurysms from patients with bicuspid aortic valve disease (n = 2) were collected as surgical waste from the Heart Hospital of Austin, Austin, Texas, and Mayo Clinic, Rochester, Minnesota. Whole mounts or adjacent sections from each specimen were examined by electron microscopy, stained for calcium phosphate, or stained with a commercially available antibody (8D10). Filtered (0.2 microm) homogenates of aneurysms were cultured and costained with 8D10 antibody followed by PicoGreen to detect DNA or incubated with [3H]uridine. Staining for calcium phosphate was heterogeneously distributed within all calcified tissues. Immunological staining with 8D10 was also heterogeneously distributed in areas with and without calcium phosphate. Analysis of areas with positive immunostaining identified spheres ranging in size from 30 to 100 nm with a spectral pattern of calcium and phosphorus (high-energy dispersive spectroscopy). Nanosized particles cultured from calcified but not from noncalcified aneurysms were recognized by a DNA-specific dye and incorporated radiolabeled uridine, and, after decalcification, they appeared via electron microscopy to contain cell walls. Therefore, nanometer-scale particles similar to those described as nanobacteria isolated from geological specimens and human kidney stones can be visualized in and cultured from calcified human cardiovascular tissue.