A5080639118- Anesthesia and Neurotoxicity Research
- Neuroscience and Neural Engineering
- Animal testing and alternatives
- 3D Printing in Biomedical Research
- Pesticide Exposure and Toxicity
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Carcinogens and Genotoxicity Assessment
- Marine Toxins and Detection Methods
- Neurogenesis and neuroplasticity mechanisms
- Computational Drug Discovery Methods
- Nuclear Receptors and Signaling
- Toxic Organic Pollutants Impact
- Cholinesterase and Neurodegenerative Diseases
- Nanoparticles: synthesis and applications
- Long-Term Effects of COVID-19
- Heavy Metal Exposure and Toxicity
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Polyomavirus and related diseases
- Trace Elements in Health
- Effects and risks of endocrine disrupting chemicals
- Traumatic Brain Injury and Neurovascular Disturbances
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
National Institute of Environmental Health Sciences
2022-2025
Johns Hopkins University
2014-2024
National Institutes of Health
2022-2024
Research Triangle Park Foundation
2024
Technical University of Denmark
2019
University of Baltimore
2016-2018
University of Konstanz
2014
Bloomberg (United States)
2013
Joint Research Centre
2006-2012
Stockholm University
2008-2011
A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching needs on one hand and opportunities provided by test systems methods other hand. Alignment academically industrially driven assay development with field DNT core mission International STakeholder NETwork...
We show that pluripotent human cells can be differentiated within an elastomer chip into a microenvironment mimicking the brain parenchyma.
This consensus statement voices the agreement of scientific stakeholders from regulatory agencies, academia and industry that a new framework needs adopting for assessment chemicals with potential to disrupt brain development. An increased prevalence neurodevelopmental disorders in children has been observed cannot solely be explained by genetics recently pre- postnatal exposure environmental suspected as causal factor. There is only very limited information on toxicity, leaving thousands...
Several shortcomings of current Parkinson's disease (PD) models limit progress in identification environmental contributions to pathogenesis. The conditionally immortalized cell line LUHMES promises make human dopaminergic neuronal cultures more easily available, but these cells are difficult culture for extended periods time. We overcame this problem by culturing them 3D with minor medium modifications. aggregates allowed penetration small molecules and sufficient oxygen nutrient supply...
Human induced pluripotent stem cells (iPSCs), together with 21st century cell culture methods, have the potential to better model human physiology, applications in toxicology, disease modeling, and study of host-pathogen interactions. Several models brain been developed recently, demonstrating cell-cell interactions multiple types physiologically relevant 3D structures. Most current models, however, lack ability represent inflammatory response because they do not include a microglial...
Background: To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and effects on neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants plasticizers are two largest market segments for they found in a wide variety products, including electronics, building materials, vehicles, furniture, car seats, plastics, textiles. As result, metabolites routinely human urine, blood, placental tissue, breast milk across globe. It...
The blood brain barrier (BBB) is the bottleneck of brain-targeted drug development. Due to their physico-chemical properties, nanoparticles (NP) can cross BBB and accumulate in different areas central nervous system (CNS), thus are potential tools carry drugs treat disorders. In vitro systems animal models have demonstrated that some NP types promote neurotoxic effects such as neuroinflammation neurodegeneration CNS. Thus, risk assessment required, but current 2D cell cultures fail mimic...
Background: Autism spectrum disorder (ASD) is a major public health concern caused by complex genetic and environmental components. Mechanisms of gene–environment (G×E) interactions reliable biomarkers associated with ASD are mostly unknown or controversial. Induced pluripotent stem cells (iPSCs) from patients clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR/Cas9)-introduced mutations in candidate genes provide an opportunity to study...
Abstract The aim of our study was to investigate whether a human neural stem cell line derived from umbilical cord blood (HUCB-NSC) can serve as reliable test model for developmental neurotoxicity (DNT). We assessed the sensitivity HUCB-NSCs at different stages panel neurotoxic (sodium tellurite, methylmercury chloride, cadmium chlorpyrifos, and L-glutamate) non-neurotoxic (acetaminophen, theophylline, D-glutamate) compounds. In addition, we investigated effect some compounds on key...
So far, only a few industrial chemicals have been identified as developmental neurotoxicants. Because the current neurotoxicity (DNT) guideline (Organisation for Economic Co-operation and Development TG 426) is based entirely on in vivo studies that are both time consuming costly, there need to develop alternative vitro methods initial screening prioritize further DNT testing. In this study, gene expression at mRNA level was evaluated determine whether could be suitable endpoint detect...
Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy. Various concerns have been raised about the possible effects of these drugs on fetal development. Current developmental neurotoxicity (DNT) testing conducted in rodents is expensive, time-consuming, and does not necessarily represent human pathophysiology. A human, vitro battery cover key events brain development could potentially overcome challenges. In this study, we assess paroxetine–...
Abstract More than 75 000 man‐made chemicals contaminate the environment; many of these have not been tested for toxicities. These demand quantitative high‐throughput screening assays to assess them causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput cytotoxicity neurons, three human neuronal cellular models were compared: SH‐SY5Y neuroblastoma cells, LUHMES conditionally‐immortalized dopaminergic Neural Stem...
Abstract Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR). Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47—the most abundant PBDE congener—with four OPFR (isopropylated phenyl phosphate—IPP, triphenyl phosphate—TPHP, isodecyl phosphate—IDDP, tricresyl phosphate (also...
Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even publication of animal-based OECD test guideline for DNT in 2007, a series non-animal technology workshops and conferences (starting 2005) shaped community that delivered comprehensive battery vitro methods (IVB). Its data interpretation is covered by very recent guidance (No. 377). Here, we aim to overview field, focusing on evolution strategies, role emerging technologies, impact...
With the finding that brown adipose tissue is present and negatively correlated to obesity in adult man, mechanism(s) of how activate humans could be important combating obesity, type 2 diabetes, their complications. In mice, main regulator nonshivering thermogenesis norepinephrine acting predominantly via β(3)-adrenergic receptors. However, vast majorities agonists have so far not been able stimulate human receptors or activity, it was postulated regulated instead by β(1)-adrenergic...
Myelin is of vital importance to the central nervous system and its disruption related a large number both neurodevelopmental neurodegenerative diseases. The differences observed between human rodent oligodendrocytes make animals inadequate for modeling these Although developing in vitro models myelinated axons has been great challenge, 3D cell cultures derived from iPSC are now available able partially reproduce myelination process. We have previously developed iPSC-derived brain organoid...