Work

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

Year: 2025

Type: article

Abstract: ABSTRACT Purpose: 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. Method 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 (Fe 2+ ), 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. Finding 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. Conclusion: These results suggest that BoNT/A is effective in preventing epileptic neuronal iron death and attenuates cognitive dysfunction through the ferroptosis pathway.

Source: Brain and Behavior

DOI: 10.1002/brb3.70930

Authors: Shuang Li, Zhi Huang, Yunqing Ma, Yake Zheng, Maiqi Du, Yajun Lian

Institutions: Zhengzhou University, First Affiliated Hospital of Zhengzhou University

Language: English

Topic: Epilepsy research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,630