Esketamine improves cognitive function in sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation.
European journal of pharmacology – November 15, 2024
Source: PubMed
Summary
Promising breakthrough: Esketamine shows potential in treating brain dysfunction caused by severe infections. The drug reduces harmful brain inflammation by calming overactive immune cells called microglia. By activating BDNF (a key brain-protective protein), esketamine helps preserve cognitive function and protect neurons from damage during sepsis-associated encephalopathy.
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.