Rosiglitazone prevents the development of kindling by modulating inflammatory cytokine production and brain cell apoptosis in mice

Background and objectives

Epileptogenesis involves complex mechanisms, including inflammation and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, possesses anti-inflammatory and neuroprotective properties. This study investigated whether rosiglitazone can prevent pentylenetetrazole (PTZ)-induced kindling in mice by modulating inflammatory cytokines and apoptosis pathways.

Methods

Male C57BL/6 mice (n = 8 per group) were assigned to sham, control, or rosiglitazone-treated groups. Kindling was induced with intraperitoneal PTZ (40 mg/kg) every 48 h for 17 days. Rosiglitazone (0.1 mg/kg) was administered 30 m before each PTZ injection. Seizure progression was monitored, and hippocampal tissues were analyzed via immunohistochemistry and Western blotting to assess cytokine levels (interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha, interferon-gamma), caspase-3 activity, and glial fibrillary acidic protein expression.

Results

Rosiglitazone significantly delayed seizure progression, reduced seizure scores, and lowered pro-inflammatory cytokine levels (IL-17A, tumor necrosis factor-alpha, interferon-gamma) while increasing IL-10. Immunohistochemical analysis revealed fewer caspase-3-positive cells and reduced glial fibrillary acidic protein expression in the treatment group compared to controls.

Conclusions

Oxidative stress and inflammation are major contributors to brain damage and neuropathology. These processes can potentially be mitigated or treated through a combination of therapeutic strategies, including neurorestorative approaches. Our findings provide compelling evidence for the anti-inflammatory and anti-apoptotic properties of rosiglitazone, suggesting its neuroprotective effects against kindling. While our study provides a robust foundation, future research involving combination therapies, such as with carbamazepine, and additional experimental approaches will be necessary to fully elucidate the therapeutic potential of rosiglitazone. Additionally, comparative studies with emerging anti-inflammatory compounds like embelin and berberine could provide deeper insights into optimal therapeutic strategies for epilepsy management. Overall, our results indicate that the protective effects of rosiglitazone are likely mediated through the reduction of inflammation and the subsequent prevention of cell death associated with inflammatory processes.

Full text

https://www.xiahepublishing.com/2572-5505/JERP-2024-00033

The study was recently published in the Journal of Exploratory Research in Pharmacology.

Journal of Exploratory Research in Pharmacology (JERP) publishes original innovative exploratory research articles, state-of-the-art reviews, editorials, short communications that focus on novel findings and the most recent advances in basic and clinical pharmacology, covering topics from drug research, drug development, clinical trials and application.

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