scholarly journals Gadolinium Retention and Deposition Revisited: How the Chemical Properties of Gadolinium-based Contrast Agents and the Use of Animal Models Inform Us about the Behavior of These Agents in the Human Brain

Radiology ◽  
2017 ◽  
Vol 285 (3) ◽  
pp. 721-724 ◽  
Author(s):  
Robert E. Lenkinski
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Contrast Agents ◽  
Chemical Properties ◽  
Gadolinium Retention

scholarly journals How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 58
Author(s):  
Quyen N. Do ◽  
Robert E. Lenkinski ◽  
Gyula Tircso ◽  
Zoltan Kovacs
Keyword(s):  
Human Brain ◽  
Chemical Properties ◽  
Point Of View ◽  
Water Soluble ◽  
Soluble Form ◽  
Clinical Implications ◽  
Kinetic Properties ◽  
Gadolinium Retention ◽  
Open Question

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

scholarly journals Is There a Brain Microbiome?

2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Ground Truth ◽  
Healthy Human ◽  
Strong Motivation ◽  
The Many ◽  
The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

Screening Breast MRI and Gadolinium Deposition: Cause for Concern?

2021 ◽  
Author(s):  
Colleen H Neal
Keyword(s):  
Breast Cancer ◽  
Renal Function ◽  
Contrast Agents ◽  
Biological Significance ◽  
Breast Mri ◽  
Reliable Data ◽  
Breast Cancer Data ◽  
Cancer Data ◽  
Contrast Enhanced ◽  
Gadolinium Retention

Abstract Gadolinium-based contrast agents (GBCAs) have been used worldwide for over 30 years and have enabled lifesaving diagnoses. Contrast-enhanced breast MRI is frequently used as supplemental screening for women with an elevated lifetime risk of breast cancer. Data have emerged that indicate a fractional amount of administered gadolinium is retained in the bone, skin, solid organs, and brain tissues of patients with normal renal function, although there are currently no reliable data regarding the clinical or biological significance of this retention. Linear GBCAs are associated with a higher risk of gadolinium retention than macrocyclic agents. Over the course of their lives, screened women may receive high cumulative doses of GBCA. Therefore, as breast MRI screening utilization increases, thoughtful use of GBCA is indicated in this patient population.

Gadolinium-Based Contrast Agents for Breast MRI and Uncertainties About Brain Gadolinium Retention

2020 ◽  
pp. 63-82
Author(s):  
Francesco Sardanelli ◽  
Simone Schiaffino ◽  
Andrea Cozzi ◽  
Luca A. Carbonaro
Keyword(s):  
Contrast Agents ◽  
Breast Mri ◽  
Gadolinium Retention

scholarly journals ‘The awesome power of yeast’ in Alzheimer’s disease research

2021 ◽  
Vol 42 (3) ◽  
pp. 130
Author(s):  
Sudip Dhakal
Keyword(s):  
Simple Model ◽  
Animal Models ◽  
Human Brain ◽  
Human Cell ◽  
Cell Biology ◽  
Experimental Studies ◽  
Disease Models ◽  
Disease Research ◽  
Research Findings ◽  
Technological Platforms

The difficulties in performing experimental studies related to diseases of the human brain have fostered a range of disease models from highly expensive and complex animal models to simple, robust, unicellular yeast models. Yeast models have been used in numerous studies to understand Alzheimer’s disease (AD) pathogenesis and to search for drugs targeting AD. Thanks to the conservation of fundamental eukaryotic processes including ageing and the availability of appropriate technological platforms, budding yeast are a simple model eukaryote to assist with understanding human cell biology, offering a platform to study human diseases. This article aims to provide insights from yeast models on the contributions of amyloid beta, a causative agent in AD, and recent research findings on AD chemoprevention.

scholarly journals Cerebral organoid model reveals excessive proliferation of human caudal late interneuron progenitors in Tuberous Sclerosis Complex

2020 ◽  
Author(s):  
Oliver L. Eichmüller ◽  
Nina S. Corsini ◽  
Ábel Vértesy ◽  
Theresa Scholl ◽  
Victoria-Elisabeth Gruber ◽  
...  
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Developmental Disorders ◽  
Neutral Loss ◽  
Egfr Signaling ◽  
Cortical Tubers ◽  
Opening Up ◽  
Excessive Proliferation

SummaryAlthough the intricate and prolonged development of the human brain critically distinguishes it from other mammals1, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models2–5. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents6. Here, we use cerebral organoids to show that overproduction of mid-gestational human interneurons causes Tuberous Sclerosis Complex (TSC), a severe neuro-developmental disorder associated with mutations in TSC1 and TSC2. We identify a previously uncharacterized population of caudal late interneuron progenitors, the CLIP-cells. In organoids derived from patients carrying heterozygous TSC2 mutations, dysregulation of mTOR signaling leads to CLIP-cell over-proliferation and formation of cortical tubers and subependymal tumors. Surprisingly, second-hit events resulting from copy-neutral loss-of-heterozygosity (cnLOH) are not causative for but occur during the progression of tumor lesions. Instead, EGFR signaling is required for tumor proliferation, opening up a promising approach to treat TSC lesions. Our study demonstrates that the analysis of developmental disorders in organoid models can lead to fundamental insights into human brain development and neuropsychiatric disorders.

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