Exacerbated immune response of the brain to peripheral immune challenge in post-septic mice

Minocycline Mitigates Sepsis-Induced Neuroinflammation and Promotes Recovery in Mice: Insights into Neuroprotection and Inflammatory Modulation

“…Consistent with earlier reports, severe weight loss and locomotor activity occurred in septic mice, a severe systemic response typically associated with septic conditions (Bardaghi et al, 2023;Salmani et al, 2022). Initially, minocycline pretreatment did not prevent these responses, resulting in minocycline-treated mice displaying a comparable degree of locomotor reduction and weight loss.…”

“…In the CLP model, M1 and M2 phenotype markers coexistence has also been reported early after sepsis induction up to 30 days (Michels et al, 2020). Our recent research further supported these findings, indicating that post-septic mice exhibit an exacerbated immune response to secondary inflammatory insults, marked by the overexpression of inflammatory mediators within the brain and heightened behavioral responses, thus suggesting fundamental changes in microglial properties in the post-septic brain (Salmani et al, 2022). We showed that pretreatment of septic mice with minocycline reduced IL-1β and TNF-α expression at 24 hours post-sepsis induction.…”

“…Furthermore, investigations utilizing animal models of sepsis have consistently demonstrated that sepsis may cause longlasting neuroinflammation and behavioral abnormalities (Bardaghi et al, 2023;Zhao et al, 2020). In a previous study, our research team observed that mice subjected to sepsis displayed heightened sensitivity to secondary inflammations, exacerbating their behavioral responses to systemic LPS injections compared to control mice (Salmani et al, 2022). Thus, the transition from acute to chronic brain inflammation following sepsis has garnered significant research attention in recent years, as preventing such a transition holds promise for averting the long-term consequences of sepsis.…”

“…Eighty-five mice were randomly divided in Control, Sepsis, Sepsis/Mino 12.5, Sepsis/Mino25 and Sepsis/Mino50 groups (n = 17 mouse/group). The sample size was chosen based on prior studies based on the primary outcome being mice revery from sepsis (Bardaghi et al, 2023;Salmani et al, 2022). A single mouse was considered as an experimental unit.…”

“…Inclusion criteria was the age and the weight of mouse and exclusion criteria was dying of mice during the experiment. Mice received intraperitoneal injection of bacterial lipopolysaccharide (LPS from E. coli O55:B5, Sigma Aldrich) in 5 mg/kg dose or an equivalent volume of saline (in the control group) to induce sepsis (Anderson et al, 2015;Salmani et al, 2022;Zhao et al, 2020). Minocycline was administered in three distinct doses (12.5, 25, and 50 mg/kg) via gavage, starting three days before LPS injection and continuing until the day of sepsis induction (Hoshino et al, 2017;Yang et al, 2022).…”