Esketamine mitigates endotoxin-induced hippocampal injury by regulating calcium transient and synaptic plasticity via the NF-α1/CREB pathway.
Neuropharmacology May 15, 2025 Mu Xu, Jialiang Wang, Jia Shi et al. 4 citations
Esketamine treatment alleviated sepsis symptoms, cognitive impairment, and decreased mortality in a mouse model of sepsis-associated encephalopathy. It reduced neuroinflammation, oxidative stress, and neuronal loss, and normalized calcium transients while improving dendritic structure and synaptic plasticity in the hippocampal CA1 region. These effects depended on the NF-α1/CREB signaling pathway, as suppressing NF-α1 abolished the protective effects and reversed improvements in calcium transients, dendrites, and post-synaptic plasticity. The findings suggest esketamine protects against hippocampal injury in sepsis through this pathway.