NCTR Division of Neurotoxicology

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Division Director: John Talpos, Ph.D.

Meet the Principal Investigators — Neurotoxicology

Ethnicity- and Gender-Related Differences in Alzheimer’s Disease

Watch the Recorded Presentation

Mission

• Identify/quantify neurotoxicity related to FDA-regulated products.
• Develop and validate quantitative biomarkers of neurotoxicity.
• Identify biological pathways of neurotoxicity.

Goals

• Provide the data and expertise necessary for crucial regulatory decisions made by FDA product centers.
• Advance regulatory science research in neurotoxicology for FDA.

Strategies

Develop the following to identify novel markers of neurotoxicity:

• Translationally valid imaging approaches
• Alternative preclinical models
• Cross-species metrics of brain function

Research Theme

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 disciplines.

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.

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2019 Select Accomplishments

Biomarkers of Brain Toxicity

Continuing to validate the use of T₂ mapping via MRI as a more sensitive and specific biomarker of neurotoxicity than ADC (apparent diffusion coefficient) mapping. T₂ relaxation is the speed at which the MRI signal disappears after initial excitation with resonant radio frequency pulse. This speed is dependent on the chemical and physical composition of the sample. In biological systems, T₂ is reproducible in normal conditions and sensitive to changes and appears to provide a higher signal-to-noise ratio, better resolution, and unidirectional changes for the detection and quantification of brain-tissue lesions. In addition, T₂ maps are easier and faster to collect than ADC maps. More information is available in the journal, Neurotoxicology.

Effects of Anesthetics on Pediatric Populations

Evaluated neural stem-cell models to predict the effects of pediatric anesthetics in combination with nitrous oxide. The research data further support the hypothesis that prolonged exposure to anesthesia, early in life, may increase the risk of developing cognitive impairments later in life. Related publications are available in the journal, Neurotoxicology.
 

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2020 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

• 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

• Using In Vitro Continuous Culture of the Human Intestinal Microbiota to Evaluate Risk Associated with Bacterial Pathogen Contamination of Fecal Microbiota Transplantation Samples

• Utilization of Neural Stem Cell Models and Biomarkers in Assessing the Developmental Neurotoxicity of Pediatric General Anesthetics

• 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

• Evaluating the Contribution of Acute Hypoxia to Models of Early Life General Anesthesia in the Rodent

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Resources for You

• NCTR Grand Rounds: "Ethnicity- and Gender-Related Differences in Alzheimer’s Disease" (Presentation recorded in Adobe Connect on January 11, 2018)
• Annual Report
• NCTR Imaging Center
• Meet the Principal Investigators

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