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Esketamine Enhances Post-Stroke Microglial Proliferation and Attenuates Neuroinflammation by Disrupting the Src-Pannexin1 Interaction

ABSTRACT: Previous research has suggested the potential of esketamine in alleviating post-stroke neuroinflammation, yet the underlying mechanism remained elusive. In our research, we have observed that esketamine increased the number of M2 anti-inflammatory phenotype microglia in the infarcted area after stroke, and this phenomenon is partly associated with the suppression of Panx1. Further research revealed that esketamine suppresses the phosphorylation of sarcoma kinase (Src) at the tyrosine 416 (Y416) site and inhibits the interaction between Src and Panx1, ultimately suppressing the function of Panx1. However, we found esketamine's inhibitory effect on post-stroke Panx1 activation is the underlying mechanism driving the increase in unactivated microglia, yet esketamine's influence on microglial polarization is mediated through a mechanism independent of Panx1.Our research suggests that esketamine, as a drug already used in clinical anesthesia, could potentially provide a solution during the periprocedural period to mitigate the damage caused by aseptic inflammation post-stroke.

ORGANISM(S): Mus musculus

PROVIDER: GSE277009 | GEO | 2024/09/17

REPOSITORIES: GEO

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