Chronic stress intensify PTZ-induced seizures by triggering neuroinflammation and oxidative stress.

Cytokines Neuroinflammation Oxidative stress PTZ-Induced seizures Restrained stress

Journal

Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516

Informations de publication

Date de publication:
01 Jul 2024
Historique:
received: 07 05 2024
revised: 27 06 2024
accepted: 28 06 2024
medline: 12 7 2024
pubmed: 12 7 2024
entrez: 11 7 2024
Statut: aheadofprint

Résumé

Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1β. Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals. The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1β in the cortex and hippocampus of mice brains. Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation.

Sections du résumé

BACKGROUND BACKGROUND
Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1β.
METHODS METHODS
Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals.
RESULTS RESULTS
The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1β in the cortex and hippocampus of mice brains.
CONCLUSIONS CONCLUSIONS
Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation.

Identifiants

pubmed: 38991397
pii: S0006-291X(24)00869-6
doi: 10.1016/j.bbrc.2024.150333
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

150333

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Jehan Zeb Khan (JZ)

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: jehanzeb@bs.qau.edu.pk.

Syeda Rida Zainab (SR)

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: zainabshah260@gmail.com.

Mujeeb Ur Rehman (MU)

Department of Pharmacy Abasyn University, Islamabad, Pakistan. Electronic address: mujeebkhawaja@gmail.com.

Muhammad Abid (M)

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: muhammadabidktk8@gmail.com.

Muhammad Usama Mazhar (MU)

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: usama_mazhar@ymail.com.

Fawad Ali Shah (FA)

Department of Pharmacology and Toxicology, College of Pharmacy Prince Sattam Bin Abdulaziz University, Al-Kharj, 16278, Saudi Arabia. Electronic address: fwd_shah@yahoo.com.

Muhammad Khalid Tipu (MK)

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: mktipu@qau.edu.pk.

Classifications MeSH