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Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: role of inflammatory response and oxidative stress

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Abstract

Seizure is paroxysmal abnormal electrical discharges in the cerebral cortex. Inflammatory pathways and oxidative stress are involved in the pathophysiology of seizures. Stress can induce an oxidative stress state and increase the production of inflammatory mediators in the brain. We investigated the effects of acute and chronic stresses on the seizure threshold in pentylenetetrazol (PTZ)-induced seizures in mice, considering oxidative stress and inflammatory mediators in the prefrontal cortex. In this study, 30 male Naval Medical Research Institute (NMRI) mice were divided into 3 groups, including acute stress, chronic stress, and control groups. PTZ was used for the induction of seizures. The gene expression of inflammatory markers (IL-1β, TNF-α, NLRP3, and iNOS), malondialdehyde (MDA) level, nitrite level, and total antioxidant capacity (TAC) were assessed in the prefrontal cortex and serum. Our results showed that stress could increase the expression of inflammatory cytokines genes and oxidative stress in the prefrontal cortex of the brain and serum following PTZ-induced seizures, which is associated with increased seizure sensitivity and decreased the seizure threshold. The effects of chronic stress were much more significant than acute stress. We concluded that the effects of chronic stress on seizure sensitivity and enhancement of neuroinflammation and oxidative stress are much greater than acute stress.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors are thankful to Dr. Sorayya Ghasemi and Dr. Gholam Reza Mobini for their contribution to this study.

Funding

This study was supported by a research grant (2831) from Shahrekord University of Medical Sciences, Shahrekord, Iran.

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  1. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Hossein Tahmasebi Dehkordi, Elham Bijad, Elham Saghaei, Mehrdad Shahrani Korrani & Hossein Amini-Khoei

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  1. Hossein Tahmasebi Dehkordi
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  2. Elham Bijad
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  3. Elham Saghaei
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  4. Mehrdad Shahrani Korrani
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Contributions

HTD, EB, ES, and HA-K performed experiments and wrote the manuscript; MS-K analyzed the data; HA-K designed the study and edited the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Hossein Amini-Khoei.

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All steps of experimentation were performed in accordance with the regulations of the University and the Guide for the Care and Use of Laboratory Animals of National Institutes of Health (Ethics code: IR.SKUMS.REC.1398.003) and Guide for the Care and Use of Laboratory Animals (8th edition, National Academies Press). Full determinations were made to reduce the use of animals and to advance their comfort.

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Dehkordi, H.T., Bijad, E., Saghaei, E. et al. Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: role of inflammatory response and oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol 396, 973–982 (2023). https://doi.org/10.1007/s00210-022-02364-7

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