Effects of Pantoprazole on PTZ-Kindling Progression and Associated Neuroinflammatory and Endoplasmic Reticulum Stress Responses in Rats
Molecular Neurobiology, cilt.63, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 63 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s12035-026-06311-y
- Dergi Adı: Molecular Neurobiology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: Endoplasmic reticulum stress, Epileptogenesis, Neuroinflammation, Pantoprazole, PTZ-kindling model
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Epileptogenesis is characterized by complex molecular changes, including neuroinflammation, endoplasmic reticulum (ER) stress, and apoptosis, contributing to seizures and associated cognitive and behavioral impairments. Pantoprazole, a proton pump inhibitor, has demonstrated anti-inflammatory and neuroprotective properties. This study investigated its effects on PTZ-kindling progression and associated molecular alterations in a pentylenetetrazole (PTZ)–induced rat model. Adult male Wistar albino rats (n = 30) were subjected to chronic PTZ kindling (30 mg/kg, i.p., on alternate day, 15 injections). Pantoprazole (5 and 10 mg/kg) or valproic acid (150 mg/kg) was administered prior to PTZ. Seizure severity was scored using the Racine scale. Cognitive and anxiety-like behaviors were assessed by passive avoidance and open field tests. Neuroinflammatory (TNF-α, NF-κB, IL-1β, COX-1/2), ER stress (GRP78, ATF4, CHOP), and apoptotic (caspase-3/9) markers were measured by ELISA in cortex and hippocampus. NF-κB, iNOS, and p-NMDAR2B expression in hippocampal CA1 and CA3 regions were evaluated immunohistochemically. Histopathological analysis was also performed. PTZ significantly increased seizure severity, memory impairment, and anxiety-like behavior, alongside elevated neuroinflammatory, ER stress, and apoptotic markers. Increased NF-κB, iNOS, and p-NMDAR2B expression and neuronal degeneration were observed in hippocampal regions. Pantoprazole dose-dependently attenuated PTZ-kindling progression, improved behavioral outcomes, and reduced the measured molecular alterations. Histopathological and immunohistochemical findings confirmed decreased neuronal damage and marker expression. Pantoprazole demonstrated protective effects in the PTZ-kindling model, which may be associated with modulation of neuroinflammatory, ER stress, apoptotic, and NMDAR2B-related pathways. These findings suggest that pantoprazole warrants further investigation as a potential adjunctive therapeutic strategy for epilepsy.