Minimally invasive measurement of carotid artery and brain temperature in the mouse.

Purpose: Brain temperature is tightly regulated and reflects a balance between cerebral metabolic heat production and heat transfer between the brain, blood, and external environment. Blood temperature and flow are critical to the regulation of brain temperature. Current methods for measuring in vivo brain and blood temperature are invasive and impractical for use in small animals.

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.

Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate.

Automated classification of cerebral arteries and veins in the neonate using ultrafast doppler spectrogram.

Cerebral arterial and venous flow (A/V) classification is a key parameter for understanding dynamic changes in neonatal brain perfusion. Currently, transfontanellar ultrasound Doppler imaging is the reference clinical technique able to discriminate between A/V using vascular indices such as resistivity index (RI) or pulsatility index (PI). However, under conditions of slow arterial and venular flow, small signal fluctuations can lead to potential misclassifications of vessels.

Disproportionate neuroanatomical effects of haploinsufficiency in adolescence compared with adulthood: links to dopamine, connectivity, covariance, and gene expression brain maps in mice.

Background: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced on neuroanatomy in the adolescent and adult mouse brain.

Methods: We examined neuronal connectivity, structural covariance, and molecular processes in a -haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute.

Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.

Background: Combination antiretroviral therapy (ART) use in pregnancy has been pivotal in improving maternal health and reducing perinatal HIV transmission. However, children born HIV-exposed uninfected fall behind their unexposed peers in several areas including neurodevelopment. The contribution of ART exposure to these deficits is not clear.

Network response of brain microvasculature to neuronal stimulation.

Neurovascular coupling (NVC), or the adjustment of blood flow in response to local increases in neuronal activity is a hallmark of healthy brain function, and the physiological foundation for functional magnetic resonance imaging (fMRI). However, it remains only partly understood due to the high complexity of the structure and function of the cerebrovascular network. Here we set out to understand NVC at the network level, i.

Polystyrene micro- and nanoplastics cause placental dysfunction in mice†.

Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106 ng/L of 5 μm polystyrene microplastics or 106 ng/L of 50 nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls.

Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model.

Background: Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model.

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.

ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for its role in ALT-positive cancers, but its role in neurological function remains elusive. Hypomorphic mutations in the X-linked ATRX gene cause a rare form of intellectual disability combined with alpha-thalassemia called ATR-X syndrome in hemizygous males.

Longitudinal Assessment of Cerebral Blood Volume Variation in Human Neonates Using Ultrafast Power Doppler and Diverging Waves.

Longitudinal assessment of brain perfusion is a critical parameter for neurodevelopmental outcome of neonates undergoing cardiopulmonary bypass procedure. In this study, we aim to measure the variations of cerebral blood volume (CBV) in human neonates during cardiac surgery, using Ultrafast Power Doppler and freehand scanning. To be clinically relevant, this method must satisfy three criteria: being able to image a wide field of view in the brain, show significant longitudinal CBV variations, and present reproducible results.

Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis.

Background: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON.

Objective: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity.

Allometric scaling relationships in mouse placenta.

Fetal growth and maturation are highly intertwined with placental development during pregnancy. Here we used placental vascular morphology measurements (depth and span) as well as the umbilical artery (UA) diameter of previously published studies on three different mouse strains (C57BL6/J, CD-1 and BALB/c), which were exposed to different conditions (combination antiretroviral therapy, chronic maternal hypoxia and malaria infection) at different embryonic days, to test the hypothesis that placental vascularization and specifically the UA size affect conceptus weight. Interaction of each study parameter with embryonic day, strain and exposure to treatments are studied to investigate the stability of the scaling relationships across and/or within strains and conditions.

Structural brain abnormalities in endothelial nitric oxide synthase-deficient mice revealed by high-resolution magnetic resonance imaging.

Introduction: Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which is essential for a variety of physiological functions in the brain. Previous work has demonstrated the detrimental effects of eNOS deficiency on brain function in male eNOS knockout (eNOS KO) mice. However, the effect of eNOS deficiency on brain structure and any association between these effects and sex is unknown.

Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a life-threatening congenital heart disease that is characterized by severe underdevelopment of left heart structures. Currently, there is no cure, and affected individuals require surgical palliation or cardiac transplantation to survive. Despite these resource-intensive measures, only about half of individuals reach adulthood, often with significant comorbidities such as liver disease and neurodevelopmental disorders.

Volumetric Fetal Flow Imaging With Magnetic Resonance Imaging.

Fetal development relies on a complex circulatory network. Accurate assessment of flow distribution is important for understanding pathologies and potential therapies. In this paper, we demonstrate a method for volumetric imaging of fetal flow with magnetic resonance imaging (MRI).

Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation.

People living with multiple sclerosis (MS) experience episodic CNS white matter lesions instigated by autoreactive T cells. With age, patients with MS show evidence of gray matter demyelination and experience devastating nonremitting symptomology. What drives progression is unclear and studying this has been hampered by the lack of suitable animal models.

Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities.

Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD-related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied.

The Effect of Three-Dimensional Whole, Major, and Small Vasculature on Mouse Brain Strain Under Both Diffuse and Focal Brain Injury Loading.

Blood vessels are much stiffer than brain parenchyma and their effects in finite element (FE) brain models need to be investigated. Despite the publication of some comprehensive three-dimensional (3D) brain vasculature models, no mechanical model exists for the mouse brain vasculature. Moreover, how the vasculature affects the mechanical behavior of brain tissue remains controversial.

The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy.

Background: Malaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling.

A functional cerebral endothelium is necessary to protect against cognitive decline.

A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included Nemo controls and three Nemo groups: One untreated, and two treated with simvastatin or exercise.

A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow.

In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term and/or have very low disease penetrance. Here, we report the development of a surgically induced mouse model of HLHS that overcomes these limitations.