Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice
Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammato...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3218452 |
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| author | Gaofei Song Huoyan Liang Heng Song Xianfei Ding Dong Wang Xiaojuan Zhang Tongwen Sun |
| author_facet | Gaofei Song Huoyan Liang Heng Song Xianfei Ding Dong Wang Xiaojuan Zhang Tongwen Sun |
| author_sort | Gaofei Song |
| collection | DOAJ |
| description | Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5′-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors. |
| format | Article |
| id | doaj-art-546d50d1bc734b87b11f0dd5da9b3a21 |
| institution | DOAJ |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-546d50d1bc734b87b11f0dd5da9b3a212025-08-20T03:20:14ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3218452Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged MiceGaofei Song0Huoyan Liang1Heng Song2Xianfei Ding3Dong Wang4Xiaojuan Zhang5Tongwen Sun6General ICUGeneral ICUGeneral ICUGeneral ICUGeneral ICUGeneral ICUGeneral ICUSepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5′-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.http://dx.doi.org/10.1155/2022/3218452 |
| spellingShingle | Gaofei Song Huoyan Liang Heng Song Xianfei Ding Dong Wang Xiaojuan Zhang Tongwen Sun Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice Journal of Immunology Research |
| title | Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice |
| title_full | Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice |
| title_fullStr | Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice |
| title_full_unstemmed | Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice |
| title_short | Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice |
| title_sort | metformin improves the prognosis of adult mice with sepsis associated encephalopathy better than that of aged mice |
| url | http://dx.doi.org/10.1155/2022/3218452 |
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