# Evaluating the Role of Inflammation in Neonatal Epileptogenesis

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $233,712

## Abstract

PROJECT SUMMARY
Seizures are a common symptom of neurologic dysfunction in the neonatal period, affecting more than 16,000
newborns in the United States per year. Over 25% of neonates with acute symptomatic seizures develop post-
neonatal epilepsy (PNE), which is often resistant to medical therapies. There is a critical need to identify those
patients most at risk for PNE and understand the mechanisms by which early seizures increase the propensity
for recurrent seizures, in hopes of identifying novel therapeutic targets in this population. There is increasing
evidence for the role of neuro-inflammation in the development of epilepsy. Levels of cytokines and micro-RNA
(miRNA) may serve as markers of disease severity and have been implicated in epileptogenesis in animal
models. Studies examining the relationship between plasma cytokine or miRNA levels with acquired epilepsy
in pediatric populations however, have not been performed. Our long-term goal is to identify those at highest
risk of developing PNE and explore novel therapeutics that may ultimately prevent epilepsy after acute brain
injury in this population. Our objective here is to evaluate plasma cytokine and miRNA levels after neonatal-
onset acute symptomatic seizures and determine their association with acute seizure severity and PNE. The
central hypothesis is that increases in specific pro-inflammatory molecules will be associated with acute
symptomatic seizure severity and subsequent development of PNE. This investigation will leverage an existing
national consortium, entitled the Neonatal Seizure Registry II (NSR II) which aims to understand the effect of
anti-seizure drug therapy after neonatal seizures on the risk of neurodevelopment and PNE. Within NSRII, we
will create a prospective cohort study with a nested case-control component, enrolling 72 neonates with acute
symptomatic seizures as well as 15 `control' subjects. Blood will be collected prior to discharge and at 2-4
months of age, then analyzed for levels of cytokines and miRNA. The diagnosis of PNE assessed at 24
months of age. Expression patterns of cytokines will be correlated with presence and severity of acute
symptomatic seizures (Aim 1), and prediction analyses performed for development of PNE (Aim 2). We will
conduct similar analyses with miRNA levels (Aim 3). As a pediatric epileptologist, my career goal is to prevent
the development of epilepsy in at-risk populations and optimize treatment regiments in those patients who do
develop epilepsy. During this award period, I will acquire expertise in registry development, advanced
immunologic methods, gene expression profiling, and bioinformatics for management of large data sets – all
necessary as I transition towards an independent investigator. This skill-set, in combination with expert
mentoring and the data I acquire here will inform a future R01 evaluating these molecular pathways in a larger
population of neonates with acute symptomatic seizures, as well as in s...

## Key facts

- **NIH application ID:** 10310461
- **Project number:** 5K23NS105918-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Adam Lawrence Numis
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $233,712
- **Award type:** 5
- **Project period:** 2018-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310461

## Citation

> US National Institutes of Health, RePORTER application 10310461, Evaluating the Role of Inflammation in Neonatal Epileptogenesis (5K23NS105918-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10310461. Licensed CC0.

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