Peripheral Transplantation of Mesenchymal Stem Cells at Sepsis Convalescence Improves Cognitive Function of Sepsis Surviving Mice

Abstract

Objective. To investigate the effects of peripheral transplantation of mesenchymal stem cells (MSCs) at sepsis convalescence on post-sepsis cognitive function and underlying mechanisms in mice. Methods. Sepsis was induced by cecal ligation and puncture (CLP) in mice. Bone marrow-derived MSCs from mice were cultured and injected via tail vein on the 8th day after CLP. Cognitive function was detected in open field, novel object recognition task, and delayed matching-to-place water maze task during 10-26 days after CLP. Neuroinflammation, neurogenesis, and peripheral inflammation were detected on the 12th and 31th days after CLP. MSCs tracing was detected during 8-10 days after CLP. Results. Transplanted MSCs were located at peripheral organs (lung, spleen, liver) and had no obvious effects on survival and weight of sepsis mice. Transplanted MSCs mitigated cognitive impairments and hippocampal microglial activation, improved hippocampal neurogenesis of sepsis surviving mice, and had no obvious effect on the leukocyte amount, the neutrophil percentage, and the inflammatory factors of peripheral blood, and the hippocampal inflammatory factors. Conclusions. Our data indicated that MSCs transplantation via peripheral vein at later phase of sepsis can improve post-sepsis cognitive impairment and hippocampal neurogenesis of sepsis surviving mice.

MSC-derived exosomal miR-140-3p improves cognitive dysfunction in sepsis-associated encephalopathy by HMGB1 and S-lactoylglutathione metabolism

“…In mice with SAE, MSCs treatment can protect the integrity of the blood‒brain barrier, reduce astrogliosis and neuroinflammation, and improve cognition and behavior 11 . Our previous research confirmed that MSCs could improve the cognitive function of mice with SAE 12 , but the specific mechanism of action is still unknown. MSCs-derived exosomes (MSCs-exo) are new candidates for cell-free therapy for various diseases 13 .…”

“…The mice were randomly divided into five groups ( n = 10): the sham group, model group, MSCs-exo + miR-140-3p mimic (Exo) group, antibiotic (ABX) group, and ABX + Exo group. The cecal ligation puncture (CLP) model was constructed 12 . In brief, animals were anesthetized with 2% sevoflurane in a well-ventilated room.…”

“…As previously described 12 , the mice were trained four times daily for 5 days. After pretraining, the mice were tested at intervals of 5 s, 20 min, and 2 h (the interval between trials 1 and 2).…”