Division Director: Sherry Ferguson, Ph.D.
The Division of Neurotoxicology focuses on increasing FDA’s understanding of the processes associated with neurotoxic outcomes—harmful effects associated with the brain and nervous system. This increased understanding may provide opportunities for improved risk assessments and identification of new approaches to diagnosis. The Division’s strategy has been to use a broad range of research approaches that capitalize on the expertise of personnel in diverse areas of neuroscience and other scientific
The Division is continually expanding its capabilities in the area of bio-imaging by adding both microPET (positron emission tomography) and MRI (magnetic resonance imaging) instruments along with trained personnel. These innovative imaging technologies give researchers a unique way to monitor brain and nervous-system activity with minimal discomfort to the study subject.
2018 Select Accomplishments
- Division scientists — in collaboration with scientists from the University of Arkansas at Fayetteville and Universidad Autonoma de San Luis Potosi and Universidad Juarez Autonoma de Tabasco in Mexico — have developed an in vitro Blood-Brain Barrier (BBB) model that simulates the BBB damage resulting from traumatic brain injury (TBI) observed in vivo. This study demonstrates the utility of the in vitro BBB model in simulating TBI and supports the use of biaxial stretch as a valuable tool to study the mechanisms of TBI and potential therapies. A manuscript describing the newly developed model was published in the January 2018 issue of Molecular Neurobiology.
- Scientists from NCTR, and the University of Arkansas for Medical Sciences have demonstrated that two commonly used chemotherapeutics (cyclophosphamide and doxorubicin), administered alone or in combination, did not induce behavioral alterations in an animal model reflective of human breast-cancer patients. The study was designed to investigate the memory and attention problems that some female breast-cancer patients experience after chemotherapy — sometimes known as “chemo” brain. The lead author of the article —Timothy Flanigan, Ph.D. — was awarded the Developmental Neurotoxicology Society’s “2018 Richard Butcher New Investigator Award” for this publication. The article is available in the April issue of Toxicological Sciences.
- NCTR scientists have successfully set up a high-throughput Mulit-Electrode Array (MEA) system to record electrical functions of brain cells as a read-out for neurotoxicity, and have demonstrated that certain neurotoxic agents can alter electrical
functions of cultured human-brain cells, such as neuronal firing rates, neuronal spikes, and electrical bursts. The MEA system is a unique emerging technology in the drug-development industry to evaluate the neurotoxicity of a drug or other compound and to predict their safety and efficacy. These NCTR studies can help support agency reviewers with validation or interpretation of MEA data submitted by industry and inform decisions about the safety and efficacy of such drug candidates.
2019 Select Research Projects
- Quantifying the importance of reactive oxygen species (ROS) and immunomodulation in drug effects — in vivo studies using zebrafish embryos
- Implementation and validation of a rodent model of traumatic brain injury
- Developmental neurotoxicity assessment of NMDA receptor antagonists in zebrafish
- Evaluation of peripheral neuropathy as a functional biomarker in a rotenone-induced rat model of Parkinson's disease
- Inveon microPET/CT and its application to in vivo monitoring of neuronal apoptosis
- Development and validation of interspecies cognitive assessments
- Functional correlates of gadolinium deposition in the rat brain
- ASK CHILDREN Study — assess specific kinds of children challenges for neurologic devices
- A search for fluidic biomarkers of neurotoxicity: Validation of observed circulating biomarkers in models of neurotoxicity and neurological disorders
- Utilization of neural stem cell models and biomarkers in assessing the developmental neurotoxicity of pediatric general anesthetics
- Evaluating the safety of ketamine treatment in young rodents as a model of human ketamine treatment
- Development of MRI imaging and informatics techniques for tissue sampling to guide and confirm classical neuropathology
- Study of vascular dysfunction in brain of two transgenic rodent models of Alzheimer’s disease (AD): Dietary impact and relevance to human AD
- Evaluation of the correlation of ethnicity-related neuroinflammation differences in Alzheimer’s disease with ER stress-induced endothelial dysfunction in the brain
- Comparison of operant performance in humans and nonhuman primates
- Evaluating the contribution of acute hypoxia to models of early life general anesthesia in the rodent
- Effects of gas anesthetics on the developing central nervous system in nonhuman primates
- Development and validation of utilizing tissue clarity techniques for neurotoxicity assessments
- Development of T2 MRI biomarkers
Resources for You
- National Center for Toxicological Research
Food and Drug Administration
3900 NCTR Rd
Jefferson, AR 72079
- (870) 543-7121