# Evaluating microglial activation as a pathogenic mechanism contributing to persistent neurological damage following acute intoxication of the juvenile brain with diisopropylfluorophosphate (DFP)

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $38,497

## Abstract

Project Summary
Diisopropylfluorophosphate (DFP) is an organophosphate (OP) cholinesterase inhibitor that is listed as a
chemical threat agent by the U.S. Department of Homeland Security. Human and animal survivors of acute OP
exposure exhibit structural brain damage and long-term impairments in learning and memory. Current research
efforts to develop more effective therapeutic strategies for treating patients acutely intoxicated with DFP is
largely focused on the adult brain and fails to address subpopulations that may be at greater risk, such as
children. The goal of this research project is to evaluate mechanisms of DFP-induced neurological damage in
the juvenile brain to inform therapeutic targets with the long-term goal of developing medical countermeasures
that will protect children in the event of a chemical emergency involving acute OP exposures. The central
hypothesis of this proposal is that acute DFP intoxication of the juvenile brain results in persistent
neurological damage that is mediated by microglial activation. To test this hypothesis, the following
specific aims will be addressed: (1) characterize the neurological sequelae in juvenile rats acutely intoxicated
with DFP; and (2) test the hypothesis that microglial activation mediates the adverse effects of acute DFP
intoxication on cognitive behavior and/or neurodegeneration. Aim 1 will be accomplished by addressing the
following sub-aims: (1a) establish the dose-response relationship of DFP-induced seizure behavior in postnatal
day (P) 28 juvenile rats; and (1b) determine whether acute DFP intoxication of the juvenile brain results in
persistent cognitive deficits and/or neurodegeneration. Aim 2 will be accomplished by addressing the following
sub-aims: (2a) establish the spatiotemporal profile of neuroinflammation following acute DFP intoxication of
P28 rats; and (2b) determine whether pharmacological attenuation of microglial activation mitigates DFP-
induced neuropathology and/or cognitive deficits.
The proposed research will be conducted at the University of California, Davis, a leading biomedical research
institution that houses a variety of centers with expertise in areas relevant to the proposed research, including
medical countermeasures against chemical threat agents, cutting-edge in vivo imaging modalities, rat
behavioral assays as they apply to neurodevelopment, and biostatistics. This environment, in combination with
the expertise of the mentor, will provide the foundation for the PI's training in developmental neurotoxicology
and neuropharmacology, advanced imaging techniques and neurobehavioral studies, quantitative science and
data analysis, teaching and mentoring, and professional development. Together, this training will be a critical
first step in the development of the PI as an independent researcher in developmental neurotoxicology.

## Key facts

- **NIH application ID:** 9988252
- **Project number:** 5F31NS110522-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Eduardo Aztlan Gonzalez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,497
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988252

## Citation

> US National Institutes of Health, RePORTER application 9988252, Evaluating microglial activation as a pathogenic mechanism contributing to persistent neurological damage following acute intoxication of the juvenile brain with diisopropylfluorophosphate (DFP) (5F31NS110522-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9988252. Licensed CC0.

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