# Botulinum Toxin Type A as a Therapeutic Agent in Epilepsy: Attenuation of Neuronal Ferroptosis and Cognitive Dysfunction

## TL;DR

Botulinum toxin type A may help treat epilepsy by reducing neuronal death and cognitive issues through a process called ferroptosis.

## Contribution

This study is the first to show that botulinum toxin type A can prevent neuronal ferroptosis and cognitive dysfunction in epilepsy models.

## Key findings

- Botulinum toxin type A reduced epileptic behavior and cognitive deficits in rats.
- The toxin protected hippocampal neurons by regulating ferroptosis markers like GPX4, ACSL4, and SLC7A11.
- In vitro experiments confirmed neuroprotective effects against magnesium-free solution-induced damage.

## Abstract

Epilepsy is one of the most common neurological disorders with no effective drugs to prevent seizures or their progression. Iron modulation is a potential advanced treatment for seizures. We aim to investigate whether botulinum toxin type A (BoNT/A) can attenuate epilepsy‐induced neuronal death and maintain cognitive function by inhibiting ferroptosis.

We established an epileptic rat model and intervened with BoNT/A to assess its influence on cognitive functions and the pathological damage of hippocampal tissues. Rat hippocampal neuronal cells were treated with magnesium‐free induction solution to establish an epileptic cell model and intervened using BoNT/A. Changes in ferrous ions (Fe2+), malondialdehyde (MDA), and glutathione (GSH) were detected in hippocampal tissues and cells. Western blot (WB) and RT‐qPCR were used to detect the protein expression of the iron death markers, including GPX4, ACSL4, and SLC7A11.

We found that BoNT/A attenuated epileptiform behavior and cognitive deficits and ameliorated hippocampal tissue damage in rats under lithium chloride‐pilocarpine‐induced epilepsy. In vitro BoNT/A treatment exerted potent neuroprotective effects on hippocampal neuronal cells treated by magnesium‐free induction solution. These protective effects were related to the regulation of ferroptosis mediated by the GPX4/ACSL4/SLC7A11 proteins.

These results suggest that BoNT/A is effective in preventing epileptic neuronal iron death and attenuates cognitive dysfunction through the ferroptosis pathway.

By establishing an epileptic rat model and in vitro epileptic cell model intervening with BoNT/A, we found that BoNT/A is effective in preventing epileptic neuronal iron death and attenuates cognitive dysfunction through the ferroptosis pathway.