Celecoxib Attenuates Brain Hippocampal Damage in PTZ-Induced Epilepsy Rats by Inhibiting NF-κB

Abstract

Background: Epileptic seizures negatively impact cognitive function and increase the levels of prostaglandins and nuclear transcription factor-κB (NF-κB) in the brain, leading to neuroinflammation. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been shown to inhibit inflammatory mediators. This study aims to determine whether celecoxib reduces the production of inflammatory mediators in status epilepticus (SE) by regulating the NF-κB pathway and has a protective effect on neurons. Methods: Male Wistar rats received 35 mg/kg/day of pentylenetetrazole (PTZ) intraperitoneally (i.p.) for 28 days. The effects of pre-treatment with celecoxib (10 mg/kg) and celecoxib plus NF-κB/p65 (p65) inhibitor, caffeic acid phenethyl ester (CAPE;15 mg/kg), against PTZ-kindled seizures were investigated. After treatment with celecoxib or celecoxib plus CAPE for 5, 10, 15 and 21 days, PTZ was injected and the seizure scores were analyzed. The hippocampus histopathology examination was completed after hematoxylin-eosin staining (H&E) staining and Nissl staining. The mRNA expression levels of PGE₂ (Prostaglandin E2), PGI₂ (Prostaglandin-I-2), and p65 were examined by real time quantitative PCR (RT-qPCR). The production of PGE₂ and PGI₂ were analyzed by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nuclear p65, total p65, and total phosphorylated p65 were determined by western blot and immunofluorescence. Results: Celecoxib treatment or celecoxib plus CAPE co-treatment after SE seizure significantly reduced the seizure scores and protected hippocampal neurons from SE damage. Celecoxib also down-regulated the mRNA expression levels of PGE₂, PGI2, and p65, as well as the reduction of PGE₂ and PFI₂ production. In addition, celecoxib significantly suppressed the protein expression levels of nuclear p65 and total phosphorylated p65. The therapeutic effects of celecoxib were more significant after CAPE down-regulated the NF-κB pathway. Conclusions: Celecoxib may inhibit the expression of PGE₂ and PGI₂ by regulating the NF-κB pathway and has a protective effect on neurons, which may appear as a promising antiepileptic drug.