# Neonatal febrile seizures: Dimethyl itaconate’s role in behavioral recovery and glutathione enzyme modulation in adult rats

**Authors:** Zohreh Ghotbeddin, Mohammad Abiri Jahromi, Ali Shahriari, Mohsen Peysokhan, Anahita Memar Dezfouli

PMC · DOI: 10.1371/journal.pone.0318430 · 2025-03-25

## TL;DR

This study shows that dimethyl itaconate reduces seizure severity and improves memory and motor skills in rats affected by febrile seizures.

## Contribution

The novel finding is that dimethyl itaconate modulates oxidative stress enzymes and enhances behavioral recovery in adult rats after neonatal febrile seizures.

## Key findings

- Dimethyl itaconate increased seizure threshold and reduced tonic-clonic seizures in rats.
- The DMI + febrile seizure group showed better memory, movement, and balance compared to the febrile seizure group.
- Dimethyl itaconate decreased oxidative stress markers like MDA and increased antioxidant enzymes like SOD and GSH.

## Abstract

Febrile seizures are common in children and can lead to neurological deficits like motor impairments, memory problems, and cognitive decline. Research on dimethyl itaconate aims to mitigate these effects and improve the quality of life for affected people. By exploring its potential as a protective agent against oxidative stress during seizures, this study in adult male rats measures the activity of key enzymes related to oxidative stress and behavioral performance. Pregnant rats were divided into control, sham, DMI, febrile seizure, and DMI +  febrile seizure groups. Seizure severity was evaluated through threshold and frequency measurements, while memory, motor function, and balance were assessed using shuttle box, rotarod, open field, and wire hanging tests. After that, the hippocampus tissue was removed from the brain and the levels of MDA, SOD, GSH, TAC, GR, GPx, and catalase were measured through biochemical methods. Results show that dimethyl itaconate raised the seizure threshold and reduced tonic-clonic seizures. The DMI +  febrile seizure group also showed improved memory, movement, and balance compared to the febrile seizure group (p < 0.05 in all cases). Overall, dimethyl itaconate decreased oxidative stress and improved neurological outcomes in fever-affected rats.

## Linked entities

- **Chemicals:** dimethyl itaconate (PubChem CID 69240), MDA (PubChem CID 1614), GSH (PubChem CID 124886), GR (PubChem CID 118706863), GPx (PubChem CID 135460989)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Gsr (glutathione-disulfide reductase) [NCBI Gene 116686], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}
- **Diseases:** cognitive decline (MESH:D003072), neurological deficits (MESH:D009461), fever (MESH:D005334), motor impairments (MESH:D000068079), memory problems (MESH:D008569), Seizure (MESH:D012640), Febrile seizures (MESH:D003294)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11936269/full.md

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Source: https://tomesphere.com/paper/PMC11936269