# Cognitive Deficits After Experimental Febrile Seizures: Neurobiology & Biomarkers

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $507,247

## Abstract

Project Summary
Epilepsy is a complex disorder which involves much more than seizures. It may also be accompanied by a
range of associated comorbid health conditions with significant health and quality of life implications as
emphasized by the National Academy of Science-sponsored Committee on the Public Health Dimensions of
the Epilepsies.1 Our research laboratories have generated a rodent model of experimental febrile status
epilepticus (eFSE), which provokes both temporal lobe epilepsy-like seizures and cognitive deficits, thereby
providing a powerful tool to probe the mechanisms underlying these conditions. Following eFSE, rats exhibit
significant deficits in the active avoidance test—a test of spatial cognition—and show altered hippocampal
oscillatory activity and abnormal temporal coding of action potentials when compared with controls. Recently,
we identified some of the mechanisms underlying epilepsy-promoting functional changes in the hippocampal
network provoked by eFSE. Specifically, we observed coordinated transcriptionally-regulated changes in the
expression of multiple genes governing neuronal behavior which resulted from eFSE-induced up-regulated
expression and function of the neuron-restrictive silencing factor (NRSF). Remarkably, our preliminary studies
indicate that both the cognitive deficits and the neuronal discoordination can be prevented by blocking NRSF
following status epilepticus. While the therapeutic implications of our findings are exciting, it is not yet known
how eFSE-induced abnormal NRSF activities contribute to disruption of gene expression and maturation of
specific cell populations throughout the circuit affected by eFSE. This proposal aims to determine the biological
underpinnings of eFSE-induced cognitive deficits at the molecular, single cell and circuit levels, and to
establish how NRSF-blockade reverses these deficits. In addition, we will determine if NRSF is involved in
memory problems associated with other developmental seizures as this will be a requisite for translation of our
discoveries. The proposed multidisciplinary, multidimensional and cutting-edge experiments will address the
mechanisms involved in eFSE-induced memory disorders and establish how such disorders can be reversed
through genetic methods. These studies will also provide novel insights into mechanisms of memory-circuit
maturation and have a potential major impact on a large population of children with febrile status epilepticus.

## Key facts

- **NIH application ID:** 10393542
- **Project number:** 5R01NS108296-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Tallie Z. Baram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $507,247
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393542

## Citation

> US National Institutes of Health, RePORTER application 10393542, Cognitive Deficits After Experimental Febrile Seizures: Neurobiology & Biomarkers (5R01NS108296-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10393542. Licensed CC0.

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