Related Experiment Video
Updated: Jul 12, 2026
Behavioral Characterization of Pentylenetetrazole-induced Seizures: Moving Beyond the Racine Scale
Published on: July 8, 2025
Resveratrol Ameliorates PTZ-Induced Seizure Activity and Diaphragm Muscle Dysfunction by Regulating Calcium Handling
Ahmet Akkoca1, Ömer Ünal2, Nilüfer Akgün-Ünal3
1Department of Biophysics, Faculty of Medicine, University of Necmettin Erbakan, Konya, Türkiye. aakkoca@erbakan.edu.tr.
Abstract:
This study aimed to investigate the chronic effects of epilepsy, a common health problem, on the diaphragm muscle and the therapeutic potential of resveratrol against these effects. Thirty-two adult male Wistar rats were divided into four groups (n = 8): Sham, resveratrol (Res, 5 mg/kg/day), pentylenetetrazol (PTZ), and PTZ + Res. Seizure activity and frequency in the epileptic groups were monitored via electrocorticography (ECoG) recordings. Diaphragmatic mechanical activities were evaluated through basal contractility and frequency-dependent fatigue parameters. Molecular analyses focused on calcium homeostasis, including tissue calcium (Ca2+) levels and sarcoplasmic/endoplasmic reticulum Ca2+-transporting ATPase 2 (Atp2a2) mRNA expression, as well as apoptotic markers (Casp-3, Casp-9, Bax, and Bcl-2). Our results indicated a significant suppression of diaphragmatic contractile parameters induced by chronic seizures, as verified by ECoG. This suppression was a consequence of Atp2a2 inhibition, Ca2+ overload, and increased apoptotic activity. On the other hand, resveratrol treatment exhibited a therapeutic effect toward restoring basal mechanical activities of the diaphragm and gaining resistance against fatigue. This effect was mediated through the reorganization of Ca2+ homeostasis and the inhibition of increased apoptotic activity. In conclusion, resveratrol demonstrated promising results in improving diaphragmatic functions in individuals with epilepsy, thanks to its role in suppressing epileptic activity, regulating Ca2+ and Atp2a2 management, and its antiapoptotic effects.
Insights
Epilepsy significantly weakens diaphragm function by disrupting calcium balance and increasing cell death. Resveratrol treatment shows promise in restoring diaphragm mechanics and function in epilepsy models.
Area of Science:
- Neurology
- Muscle Physiology
- Pharmacology
Background:
- Epilepsy is a common neurological disorder with potential systemic effects.
- Diaphragm muscle dysfunction is a recognized complication of chronic epilepsy.
- Calcium homeostasis and apoptosis play critical roles in muscle function.
Purpose of the Study:
- To investigate the chronic impact of epilepsy on diaphragm muscle function.
- To evaluate the therapeutic potential of resveratrol in mitigating these effects.
- To elucidate the molecular mechanisms underlying resveratrol's action.
Main Methods:
- Adult male Wistar rats were divided into Sham, resveratrol, pentylenetetrazol (PTZ)-induced epilepsy, and PTZ+resveratrol groups.
- Seizure activity was monitored using electrocorticography (ECoG).
- Diaphragm contractility, fatigue, calcium levels, Atp2a2 expression, and apoptotic markers were assessed.
Main Results:
- Chronic seizures significantly impaired diaphragm contractility and induced fatigue.
- Seizure-induced diaphragm dysfunction was linked to Atp2a2 inhibition, calcium overload, and increased apoptosis.
- Resveratrol treatment improved diaphragm mechanical activity and fatigue resistance.
- Resveratrol's effects were associated with normalized calcium homeostasis and reduced apoptosis.
Conclusions:
- Epilepsy leads to diaphragm dysfunction through impaired calcium handling and apoptosis.
- Resveratrol demonstrates therapeutic potential by restoring diaphragm function in epilepsy.
- Resveratrol exerts its beneficial effects by regulating calcium homeostasis, Atp2a2 activity, and apoptosis.
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