Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli
Background: Microglial activation after systemic infection has been suggested to mediate sepsis-associated delirium. A systematic review of animal studies suggested distinct differences between microglial activation after systemic challenge with live bacteria and lipopolysaccharide (LPS). Here, we d...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2018.00110/full |
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| author | Inge C. M. Hoogland Dunja Westhoff Joo-Yeon Engelen-Lee Jeroen Melief Mercedes Valls Serón Judith H. M. P. Houben-Weerts Inge Huitinga David J. van Westerloo Tom van der Poll Willem A. van Gool Diederik van de Beek |
| author_facet | Inge C. M. Hoogland Dunja Westhoff Joo-Yeon Engelen-Lee Jeroen Melief Mercedes Valls Serón Judith H. M. P. Houben-Weerts Inge Huitinga David J. van Westerloo Tom van der Poll Willem A. van Gool Diederik van de Beek |
| author_sort | Inge C. M. Hoogland |
| collection | DOAJ |
| description | Background: Microglial activation after systemic infection has been suggested to mediate sepsis-associated delirium. A systematic review of animal studies suggested distinct differences between microglial activation after systemic challenge with live bacteria and lipopolysaccharide (LPS). Here, we describe a mouse model of microglial activation after systemic challenge with live Escherichia coli (E. coli) and compare results with systemic challenge with LPS.Methods: Sixty mice were intraperitoneally injected with E. coli (1 × 104 colony-forming units) and sacrificed at 12, 20, 48, and 72 h after inoculation. For 48 and 72 h time points, mice were treated with ceftriaxone. Thirty mice were intraperitoneally injected with LPS (5 mg/kg) and sacrificed 3 and 48 h after inoculation; 48 control mice were intraperitoneally injected with isotonic saline. Microglial response was monitored by immunohistochemical staining with Iba-1 antibody and flow cytometry; and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators.Results: Mice infected with live E. coli showed microglial activation 72 h post-inoculation, with increased cell number in cortex (p = 0.0002), hippocampus (p = 0.003), and thalamus (p = 0.0001), but not in the caudate nucleus/putamen (p = 0.33), as compared to controls. At 72 h, flow cytometry of microglia from E. coli infected mice showed increased cell size (p = 0.03) and CD45 expression (p = 0.03), but no increase in CD11b expression, and no differences in brain mRNA expression of inflammatory mediators as compared to controls. In mice with systemic LPS stimulation, microglial cells were morphologically activated at the 48 h time point with increased cell numbers in cortex (p = 0.002), hippocampus (p = 0.0003), thalamus (p = 0.007), and caudate nucleus/putamen (p < 0.0001), as compared to controls. At 48 h, flow cytometry of microglia from LPS stimulated mice showed increased cell size (p = 0.03), CD45 (p = 0.03), and CD11b (p = 0.04) expression. Brain mRNA expression of TNF-α (p = 0.02), IL-1β (p = 0.02), and MCP-1 (p = 0.03) were increased as compared to controls.Interpretation: Systemic challenge with live E. coli causes a neuro-inflammatory response, but this response occurs at a later time point and is less vigorous as compared to LPS stimulation.The E. coli model mimics the clinical situation of infection associated delirium more closely than stimulation with supra-natural LPS. |
| first_indexed | 2024-04-12T09:18:28Z |
| format | Article |
| id | doaj.art-91a8d9dfa4fe468c8723a19ba8fe8c93 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T09:18:28Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-91a8d9dfa4fe468c8723a19ba8fe8c932022-12-22T03:38:45ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-04-011210.3389/fncel.2018.00110352494Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coliInge C. M. Hoogland0Dunja Westhoff1Joo-Yeon Engelen-Lee2Jeroen Melief3Mercedes Valls Serón4Judith H. M. P. Houben-Weerts5Inge Huitinga6David J. van Westerloo7Tom van der Poll8Willem A. van Gool9Diederik van de Beek10Department of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsNetherlands Institute for Neuroscience - KNAW, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsNetherlands Institute for Neuroscience - KNAW, Amsterdam, NetherlandsIntensive Care Medicine, Leiden University Medical Center, Leiden, NetherlandsCenter of Experimental Molecular Medicine, Academic Medical Center, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Neurology, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsBackground: Microglial activation after systemic infection has been suggested to mediate sepsis-associated delirium. A systematic review of animal studies suggested distinct differences between microglial activation after systemic challenge with live bacteria and lipopolysaccharide (LPS). Here, we describe a mouse model of microglial activation after systemic challenge with live Escherichia coli (E. coli) and compare results with systemic challenge with LPS.Methods: Sixty mice were intraperitoneally injected with E. coli (1 × 104 colony-forming units) and sacrificed at 12, 20, 48, and 72 h after inoculation. For 48 and 72 h time points, mice were treated with ceftriaxone. Thirty mice were intraperitoneally injected with LPS (5 mg/kg) and sacrificed 3 and 48 h after inoculation; 48 control mice were intraperitoneally injected with isotonic saline. Microglial response was monitored by immunohistochemical staining with Iba-1 antibody and flow cytometry; and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators.Results: Mice infected with live E. coli showed microglial activation 72 h post-inoculation, with increased cell number in cortex (p = 0.0002), hippocampus (p = 0.003), and thalamus (p = 0.0001), but not in the caudate nucleus/putamen (p = 0.33), as compared to controls. At 72 h, flow cytometry of microglia from E. coli infected mice showed increased cell size (p = 0.03) and CD45 expression (p = 0.03), but no increase in CD11b expression, and no differences in brain mRNA expression of inflammatory mediators as compared to controls. In mice with systemic LPS stimulation, microglial cells were morphologically activated at the 48 h time point with increased cell numbers in cortex (p = 0.002), hippocampus (p = 0.0003), thalamus (p = 0.007), and caudate nucleus/putamen (p < 0.0001), as compared to controls. At 48 h, flow cytometry of microglia from LPS stimulated mice showed increased cell size (p = 0.03), CD45 (p = 0.03), and CD11b (p = 0.04) expression. Brain mRNA expression of TNF-α (p = 0.02), IL-1β (p = 0.02), and MCP-1 (p = 0.03) were increased as compared to controls.Interpretation: Systemic challenge with live E. coli causes a neuro-inflammatory response, but this response occurs at a later time point and is less vigorous as compared to LPS stimulation.The E. coli model mimics the clinical situation of infection associated delirium more closely than stimulation with supra-natural LPS.http://journal.frontiersin.org/article/10.3389/fncel.2018.00110/fullmicrogliamicroglial activationsystemic infectionlipopolysaccharideEscherichia colineuro-inflammation |
| spellingShingle | Inge C. M. Hoogland Dunja Westhoff Joo-Yeon Engelen-Lee Jeroen Melief Mercedes Valls Serón Judith H. M. P. Houben-Weerts Inge Huitinga David J. van Westerloo Tom van der Poll Willem A. van Gool Diederik van de Beek Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli Frontiers in Cellular Neuroscience microglia microglial activation systemic infection lipopolysaccharide Escherichia coli neuro-inflammation |
| title | Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli |
| title_full | Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli |
| title_fullStr | Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli |
| title_full_unstemmed | Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli |
| title_short | Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli |
| title_sort | microglial activation after systemic stimulation with lipopolysaccharide and escherichia coli |
| topic | microglia microglial activation systemic infection lipopolysaccharide Escherichia coli neuro-inflammation |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2018.00110/full |
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