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

  • سال انتشار: 1401
  • محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 25، شماره: 6
  • کد COI اختصاصی: JR_IJBMS-25-6_004
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 167
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نویسندگان

Mina Ranjbaran

Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Farzaneh Kianian

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Mehri Kadkhodaee

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Behjat Seifi

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Ghorbangol Ashabi

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Fariba Akhondzadeh

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Maryam Adelipour

Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Maryam Izad

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Kamal Abdolmohammadi

Department of Immunology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran

چکیده

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.

کلیدواژه ها

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

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