# Diversity Supplement to UC Davis CounterACT Center of Excellence: Role of IL-1β in mediating the chronic adverse neurological effects of acute organophosphate intoxication.

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $14,751

## Abstract

Abstract
Convulsant chemical threat agents, such as the organophosphates (OPs) diisopropylfluorophosphate (DFP) and
soman, can trigger seizures that progress to life-threatening status epilepticus (SE). Survivors face significant,
long-term morbidity, including spontaneous recurrent seizures (SRS) and mild-to-severe memory loss. Current
medical countermeasures fail to sufficiently protect against these long-term neurological deficits. The work
described in this Diversity supplement will use a well-established rat model of acute DFP intoxication to test the
hypothesis that administering therapies that antagonize interleukin-1β (IL-1β) signaling as adjuncts to standard
of care will mitigate the long-term, adverse neurological consequences of acute OP intoxication. The scientific
premise for this hypothesis includes clinical and experimental evidence that: (1) IL-1β levels are predictive of
epileptogenesis in patients with traumatic brain injury; (2) Anakinra, a commercially available recombinant human
IL-1R antagonist (IL1Ra) used to treat autoimmune disorders, is anti-epileptogenic in experimental models; (3)
In clinical trials, anakinra successfully reduced unremitting seizures in both the acute and chronic disease phases
of FIRES (Febrile Infection-Related Epilepsy Syndrome); and (4) Anakinra reduced drug-resistant seizures in
adolescents with epilepsy associated with an inflammatory etiology. The research goals of this Diversity
supplement are to: (1) Characterize the spatiotemporal profile of IL-1β signaling in the brain of male and female
rats following acute DFP intoxication in order to determine therapeutic windows, and develop translatable
biomarkers of inflammation that predict SRS and/or cognitive dysfunction and (2) Evaluate the neuroprotective
efficacy of anakinra in male and female rats acutely intoxicated with DFP. This research is complementary to
and extends the research described in the parent grant, which is focused on lipid mediators of neuroinflammation
as therapeutic targets. The training goals of this Diversity supplement include: (1) Develop the trainee’s
knowledge and technical skill set to enable them to successfully conduct research on medical countermeasures;
(2) Guide the trainee’s research activity to ensure the generation of data needed to support their preparation of
a competitive F31 application and advance to candidacy, was well as inform the feasibility of therapeutically
targeting IL-1β signaling to mitigate the long-term adverse neurological consequences of acute OP intoxication;
(3) Enhance the trainee’s professional skills; and (4) Actively work with the trainee to build their professional
networks to enhance their likelihood of transitioning to an independent career in academic research.

## Key facts

- **NIH application ID:** 10837432
- **Project number:** 3U54NS127758-01S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Amy R. Brooks-Kayal
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $14,751
- **Award type:** 3
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837432

## Citation

> US National Institutes of Health, RePORTER application 10837432, Diversity Supplement to UC Davis CounterACT Center of Excellence: Role of IL-1β in mediating the chronic adverse neurological effects of acute organophosphate intoxication. (3U54NS127758-01S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10837432. Licensed CC0.

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