neuroprotective effects of semaglutide in endotoxemia mouse model

Aims: the present study aimed to examine the neuroprotective effects of semaglutide during endotoxemia and its role in modulating pro-inflammatory mediators.materials & methods: twenty-four adult male swiss albino mice, 8-12 weeks old, weighing 25-35g, were randomly divided into four equal groups (n=6), including sham (laparotomy without cecal ligation and puncture, sepsis (laparotomy with clp), vehicle (equivalent volume of distilled water before clp), and semaglutide (40µg/kg/day before clp). the brain was used for tissue evaluation of tnf-α, il-6, il-1β, tlr4, and p-stat3, as well as for histological examination.findings: the tissue levels of tnf-α, il-6 and il-1β in the sham group were significantly lower than the sepsis and vehicle groups (p<0.05). in the semaglutide group, tissue levels of tnf-α, il-6, and il-1β were significantly lower than the sepsis and vehicle groups (p<0.05). the tissue levels of tlr4 and stat3 in the sham group were significantly lower than the sepsis and vehicle groups (p<0.05). also, tissue levels of tlr4 and stat3 in the semaglutide group were significantly lower than the sepsis and vehicle groups (p<0.05). histopathologically, semaglutide considerably reduced brain damage compared to the sepsis and vehicle groups.conclusion: semaglutide can reduce brain dysfunction during clp-induced polymicrobial sepsis in male mice through its modulating effects on tlr4stat3 downstream signaling pathways and subsequently reducing inflammatory cytokines tnf-α, il-6, and il-1β.