Esketamine improves cognitive function in sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation.

Esketamine improves cognitive impairments and alleviates neuronal damage in mice with sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation. The beneficial effects of Esketamine on microglia and cognitive behavior were counteracted by the BDNF receptor antagonist K252a in both in vivo and in vitro experiments. These results suggest that Esketamine inhibits microglia-mediated neuroinflammation by activating the BDNF pathway, thereby mitigating neuronal damage and cognitive dysfunction associated with sepsis-associated encephalopathy.

Study at a glance

Abstract

Microglia-mediated neuroinflammation is critical in the pathogenesis of sepsis-associated encephalopathy(SAE). Identifying the key factors that inhibit microglia-mediated neuroinflammation holds promise as a potential target for preventing and treating SAE. Esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been proposed to possess protective and therapeutic properties against neuroinflammatory disorders. This study provides evidence that the administration of Esketamine in SAE mice improves cognitive impairments and alleviates neuronal damage by inhibiting the microglia-mediated neuroinflammation. The BDNF receptor antagonist K252a was employed in both vivo and in vitro experiments. The findings indicate that K252a successfully counteracted the beneficial effects of Esketamine on microglia and cognitive behavior in mice with SAE. Consequently, these results suggest that Esketamine inhibits microglia-mediated neuroinflammation by activating the BDNF pathway, and mitigating neuronal damage and cognitive dysfunction associated with SAE.