The translocator protein antagonist ONO-2952 attenuates neuroinflammation and neuronal apoptosis in an epilepsy rat model

Abstract

Epilepsy is a globally prevalent chronic neurological disorder, and translocator protein 18 kDa (TSPO)-mediated neuroinflammation plays a critical role in epilepsy pathogenesis. This study aimed to explore the effect of the translocator protein 18 kDa antagonist ONO-2952 on neuroinflammation and cognitive function in epilepsy by establishing a mature epileptic rat model, which was divided into control group, untreated status epilepticus group and ONO-2952 intervention status epilepticus group; cognitive and behavioral tests were performed to observe the behavioral changes of rats, immunofluorescence staining was used to detect neuronal apoptosis, flow cytometry was adopted to analyze immune cell infiltration, and Western blotting was applied to measure the expression of proinflammatory cytokines. The results showed that ONO-2952 could down-regulate the expression of translocator protein 18 kDa, reduce the level of proinflammatory cytokines and peripheral immune cell infiltration, thereby inhibiting neuroinflammation in epileptic rats, and it could also relieve hippocampal neuronal apoptosis and effectively improve the cognitive dysfunction of model rats. This study confirms that ONO-2952 can regulate the expression of translocator protein 18 kDa, inhibit neuroinflammation and neuronal apoptosis, and improve cognitive function in epileptic rats, and further research is required to fully elucidate its specific biological effects.