The Involvement of the Keap1-Nrf2 Pathway in Seizure-like Activity Model

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen species and antioxidant defenses. The brain is extremely intolerant to oxidative stress because of its high oxygen demand. Reactive oxygen species (ROS), the most important oxygen free radical, is closely related to the pathology and development of various neurodegenerative diseases. Excessive ROS production disrupts the balance between cellular oxidation and antioxidant defense systems, induces lipid peroxidation, DNA fragmentation, cellular integrity, and functional impairment, and ultimately leads to neuronal function disruption and apoptosis.

Epilepsy is still a major medical concern with no cure. Several studies have shown that oxidative stress plays an important role in epilepsy pathogenesis and may represent a target for the treatment of epilepsy. To overcome this physiological stress, cells are equipped with elaborate defense systems that allow them to maintain homeostasis in an ever-changing environment. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) plays a central role in the inducible cytoprotective response to oxidative insults. Recent studies have suggested that Nrf2 binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative damage and accumulation of toxic metabolites. Therefore, our research aim is to evaluate the role of the Keap1-Nrf2 pathway in seizure-like activity model and to further investigate the skin-brain axis.