# The Role of the Adaptive Immune System in Epilepsy

> **NIH NIH R21** · CREIGHTON UNIVERSITY · 2021 · $383,480

## Abstract

Project Summary
The lack of drug effectiveness in refractory epilepsy (~30% of peoplw with epilepsy) implies the existence of
additional mechanisms of hyperexcitability and hypersynchrony that current anti-seizure drugs do not target.
The long-term goals of our research program are to identify novel molecular targets with disease-modifying
effects for the treatment of refractory epilepsy, which may also decrease co-morbidities and increase longevity
in those susceptible to SUDEP. In the past decade, inflammation has been found to have a detrimental impact
on epilepsy. A minority of studies have focused on peripheral immune responses but have found that severe
human and animal refractory epilepsies exhibit a chronic CNS inflammatory state with activation and infiltration
of peripheral adaptive immune cells into the brain. However, the relationship between chronic epilepsy and the
peripheral adaptive immune system is unknown. The objective of this grant is to determine the role of
peripheral adaptive immune response in seizure generation, seizure severity and epileptogenesis. The central
hypothesis is that epileptic seizures cause activation of the peripheral adaptive immune response and that
seizure-induced peripheral adaptive immune responses contribute to worsening seizures/epilepsy. Our
rationale is that delineating the nature of the relationship between chronic epilepsy and the peripheral adaptive
immune system will offer new research avenues and therapeutic opportunities. Our specific aims will test the
following hypotheses: (Aim 1) Spontaneous recurrent seizures in chronic epilepsy alter the peripheral immune
response resulting in brain infiltration of peripheral immune cells; and (Aim 2) Peripheral adaptive immune cells
contribute to the age-dependent worsening of seizure severity in epileptic mice. Upon conclusion, we will
understand seizures in the setting of peripheral inflammation. The proposed research is innovative because we
investigate the effect of spontaneous recurrent seizures on peripheral inflammatory signaling and vice versa in
a developmental model of temporal lobe epilepsy, a heretofore-unexamined process.

## Key facts

- **NIH application ID:** 10128583
- **Project number:** 1R21NS114741-01A1
- **Recipient organization:** CREIGHTON UNIVERSITY
- **Principal Investigator:** Kristina A Simeone
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,480
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128583

## Citation

> US National Institutes of Health, RePORTER application 10128583, The Role of the Adaptive Immune System in Epilepsy (1R21NS114741-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128583. Licensed CC0.

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