# The role of oxidative stress and inflammation in epileptogenesis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $352,188

## Abstract

SUMMARY
The large heterogeneity of epileptic syndromes and their underlying pathophysiology represent a particular
challenge to the development of pathway-specific therapies for epilepsy prevention. In many people, epilepsy
is produced by specific brain “insults”, such as trauma, infarcts, or episodes of prolonged status epilepticus
(SE), while in others, epilepsy is a result of a primary genetic abnormality producing either structural or
functional alterations in the developing brain. In all cases, patients are at high risk for developing epilepsy.
Studies in the last decade have contributed to the view that there is an important link between oxidative stress,
inflammation and epilepsy, such that seizures can induce oxidative stress and inflammation, but also that
oxidative stress and enhanced pro-inflammatory signals in the brain contribute to epilepsy progression. Recent
animal and human studies have identified a potential novel target that may be a central component of a
cascade of such processes - the nuclear factor erythroid 2-related factor 2 (Nrf2). This transcription factor
promotes the expression of multiple protective antioxidant and anti-inflammatory proteins. The major objective
of this project is to determine whether dimethyl fumarate (DMF), a Nrf2 inducer that uniquely reduces oxidative
stress and inflammation and is approved for other clinical indications, can prevent epilepsy in two distinct
mouse models of epileptogenesis. To increase the translational potential of our study, we will also determine
whether select systemic biomarkers of oxidative stress and inflammation are able to predict the development of
epilepsy and epilepsy-associated co-morbidities (prognostic biomarkers) and monitor the acute response to
treatment (pharmacodynamic biomarkers). Aim 1 will use long-term video EEG recordings of seizures and
behavioral testing to determine whether DMF, when administered following induction of SE, will reduce the
incidence and severity of epilepsy and reduce the associated behavioral comorbidities. Using
immunohistochemical and biochemical methods, Aim 2 will assess changes in proteins associated with redox
modulation, inflammation and cytokine signaling in the brain and plasma following DMF treatment in the same
model, with the hypothesis that mediators that most strongly associate with disease progression will be more
affected by treatment than the ones that are not. Finally, to examine whether there is more generalizable
applicability of this drug to other epilepsies, in Aim 3 we will determine whether DMF can prevent or delay the
development of epilepsy in a tuberous sclerosis model of epilepsy and cognitive dysfunction.

## Key facts

- **NIH application ID:** 10143315
- **Project number:** 5R01NS101156-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Delia Talos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,188
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143315

## Citation

> US National Institutes of Health, RePORTER application 10143315, The role of oxidative stress and inflammation in epileptogenesis (5R01NS101156-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143315. Licensed CC0.

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