# Targeting Microglia in Febrile Status Epilepticus

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $545,200

## Abstract

PROJECT SUMMARY
Febrile seizures are the most common form of childhood seizures. They affect 2-5% of children
between the ages of 6 and 60 months. They occur with a rise in body temperature that is often
associated with a fever, though the underlying mechanisms are not fully understood. In a subset of
children with febrile seizure, seizures and convulsions are prolonged and are referred to as febrile
status epilepticus (fSE). Some children that experience fSE go on to develop epilepsy in childhood or
adulthood making childhood fSE a risk factor for subsequently developing epilepsy. Although the
underlying mechanisms governing status epilepticus and epilepsy are known to emanate from
neuronal dysfunction, compelling research in recent years suggest contributions from inflammation,
broadly characterized, in fSE. This is evidenced by increased inflammatory mediators in fSE and
reduced SE with broad-acting anti-inflammatory drugs. However, inflammation, can be generated by
resident cells of the brain such as microglia and astrocytes as well as peripheral immune cells that
can release inflammatory mediators outside the brain to alter neuronal function. Current research has
thus far failed to delineate cell-specific contributions to inflammation in the context of fSE. In this
project, we have begun to determine distinct contributions from microglia, the primary resident
immune cell of the brain, in fSE. Given broadly detrimental roles for inflammation in fSE, it has been
assumed that microglia, as inflammation-competent cells, promote fSE. Contrary to this assumption,
our preliminary experimental results in both chemical- and hyperthermia- induced SE, indicate that
microglia actually play beneficial roles in reducing SE severity in mouse models. Moreover, we have
identified the microglial-specific P2Y12R as a candidate regulator of microglial beneficial contributions
during experimental SE. Therefore, using well-established microglial elimination approaches, we will
now: (1) test for general microglial roles in hyperthermia-induced SE and determine whether
microglial regulate the neuroinflammatory environment in SE (Aim 1); (2) test for specific microglial
P2Y12R roles in regulating microglial beneficial contributions to controlling hyperthermia-induced SE
(Aim 2); and (3) determine microglial P2Y12R roles in the progression to temporal lobe epilepsy
(TLE) using a novel mouse model follow early life exposure to hyperthermia-induced SE (Aim 3). This
project is a first to adequately clarify microglial contributions in a mouse model of fSE as a pre-clinical
model. This work will provide a framework for targeting microglia as a novel approach to ameliorate
SE in general and fSE in particular.

## Key facts

- **NIH application ID:** 10439870
- **Project number:** 5R01NS119243-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ukpong Bassey Eyo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $545,200
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439870

## Citation

> US National Institutes of Health, RePORTER application 10439870, Targeting Microglia in Febrile Status Epilepticus (5R01NS119243-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439870. Licensed CC0.

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