RESUMO
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.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Sepse , Animais , Cognição , Convalescença , Camundongos , Camundongos Endogâmicos C57BL , Sepse/complicações , Sepse/terapiaRESUMO
The prevention and treatment of sepsis associated encephalopathy (SAE) remains challenging in clinic. Besides the anti-infection treatments and goal-directed supportive treatments, no specific method is reported for the prevention and treatment of SAE. This study tried to investigate the effects and underlying mechanisms of small dose of L-dopa/Benserazide hydrochloride (L-DA) on SAE. We found that L-DA administration (i.p.) at early stage of sepsis, but not at late stage, improved learning and memory of sepsis surviving mice in Cecal ligation and perforation (CLP) model. Corresponding to the improvement of learning and memory in CLP model, L-DA administration limited neuroinflammation, improved neuroplasticity, reversed sepsis-induced decrease of hippocampal dopamine level, but had no obvious effects on the survival and body weight recovery. Further studies showed that specific inhibitors of dopamine D1 or D2 receptors both partly reduced the protective effect of L-DA on the learning and memory of lipopolysaccharides (LPS) treated mice. D1 receptor specific inhibitor significantly blocked the anti-neuroinflammation effects of L-DA in LPS treated mice, but D2 receptor inhibitor did not. All these suggest that L-DA administration could prevent and treat SAE via dopamine D1 and D2 receptors. Dopamine D1 receptor is a potential target of anti-neuroinflammation.