Mesenchymal stem cells and their conditioned medium as potential therapeutic strategies in managing comorbid anxiety in rat sepsis induced by cecal ligation and puncture

Objective(s): Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis. Due to the beneficial effects of mesenchymal stem cells (MSCs) therapy on anxiety, an extreme and early manifestation of SAE, we hypothesized that MSCs-derived conditioned medium (CM) may be able to attenuate anxiety in cecal ligation and puncture (CLP)-induced sepsis.Materials and Methods: Rats were assigned into ۴ groups: sham, CLP, MSC, and CM. All animals, except in the sham group, underwent the CLP procedure to induce sepsis. Two hours after sepsis induction, the rats in MSC and CM groups, received ۱×۱۰۶ MSCs and CM derived from the same number of cells, respectively. ۴۸ hr after the treatments, anxiety-related behaviors were assessed, and brain and right hippocampal tissues were collected.Results: MSCs and CM enhanced the percentages of open arm entries and time spent in the open arms of the elevated plus-maze and the time spent in the light side of the light-dark box. MSCs and CM decreased the Evans blue content and decreased the IL-۶ and TNF-α levels in the brain tissue samples. Reductions in the expression of ۵-HT۲A receptors and phosphorylation of ERK۱/۲ and an increase in the expression of ۵-HT۱A receptors in the hippocampal tissue samples were observed in the MSC and CM groups.Conclusion: MSCs and MSCs-derived CM attenuated anxiety-related behaviors to an equal extent by reducing inflammation, modifying ۵-HT receptor expression changes, and inhibiting the ERK pathway. Therefore, MSCs-derived CM may be considered a promising therapy for comorbid anxiety in septic patients.

Keywords:

Extracellular signal-regulated kinases , Inflammation , Sepsis , Sepsis-associated-encephalopathy , Serotonin