# Brain-invading monocytes promote the deleterious consequences of status epilepticus

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $341,250

## Abstract

Project Summary/Abstract
Status epilepticus (SE) is a frequent neurological emergency that can reduce the quality of life of those
affected, produce cognitive deficits, and result in the development of epilepsy. Brain inflammation is an
invariable feature of seizure activity and is believed to contribute to neuronal demise and exacerbate the
deleterious behavioral consequences of unabated seizures. However, the involvement of blood-borne immune
cells in the brain's inflammatory reaction after seizures remains unresolved. We have recently identified a
subclass of circulating monocytes that invades brain tissue after seizures. Our findings indicate that blocking
monocyte infiltration, via Ccr2 knockout, reduces the deleterious consequences of SE. These results prompt us
to ask whether brain-invading monocytes are a novel therapeutic target to attenuate the adverse effects of
seizures, alleviate cognitive dysfunction, and inhibit the development of epilepsy after SE.
My hypothesis is that microglia-driven recruitment of brain-invading monocytes is a strong driver of SE-induced
neurobehavioral deficits and epileptogenesis in the weeks following SE because pro-inflammatory monocytes
migrate across the BBB promoting albumin extravasation into the brain. The lessons gleaned from completion
of the proposed studies will lead to insights into myeloid cell biology in epilepsy as well as brain disease in
general. The proposed studies will determine how the peripheral immune system can impact central immune
reactions and contribute to co-morbidities, leading to decreased quality of life in individuals afflicted with
epilepsy. Utilizing multiple techniques, my specific aims are designed to investigate and validate important
components of this hypothesis.
Aim 1. To test the hypothesis that brain-infiltrating monocytes engraft in the brain and maintain their
 own pro-inflammatory profile, exacerbating a pro-inflammatory response in microglia.
Aim 2. To test the hypothesis that albumin extravasation is reliant on monocyte migration across the
BBB.
Aim 3. To determine if blocking monocyte brain entry exerts antiepileptogenic or disease modifying
 effects after SE.
If our aims are achieved, then this would support continued efforts for targeting peripheral monocytes with
therapies, which could have a significant impact on reducing the burden of neurological disease, a major
mission of NINDS.

## Key facts

- **NIH application ID:** 10303046
- **Project number:** 5R01NS112350-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Nicholas Varvel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $341,250
- **Award type:** 5
- **Project period:** 2019-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10303046

## Citation

> US National Institutes of Health, RePORTER application 10303046, Brain-invading monocytes promote the deleterious consequences of status epilepticus (5R01NS112350-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10303046. Licensed CC0.

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