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Monocyte chemoattractant protein-1-deficiency impairs the expression of IL-6, IL-1β and G-CSF after transient focal ischemia in mice.

Strecker JK, Minnerup J, Gess B, Ringelstein EB, Schäbitz WR, Schilling M - PLoS ONE (2011)

Bottom Line: Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells.Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia.These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Münster, Münster, Germany. strecker.jan@gmx.de

ABSTRACT
Monocyte chemoattractant protein-1 (MCP-1), a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1) performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2) analyzed a possible impact of MCP-1 on astrocyte activation (3) investigated the cellular origin of respective inflammatory cytokines and (4) analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

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MCP-1-deficiency has no impact on astrocyte activation.Whole hemisphere GFAP-stained images comparing the activation of astrocytes between wildtype and MCP-1-deficient animals. Analyses showed no differences with respect to immunoreactivity and morphology between wildtype and MCP-1-deficient mice. GFAP staining showed the common distribution and activation of astrocytes reacting to oxygen deprivation. Astrogliosis occurred primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice.
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pone-0025863-g002: MCP-1-deficiency has no impact on astrocyte activation.Whole hemisphere GFAP-stained images comparing the activation of astrocytes between wildtype and MCP-1-deficient animals. Analyses showed no differences with respect to immunoreactivity and morphology between wildtype and MCP-1-deficient mice. GFAP staining showed the common distribution and activation of astrocytes reacting to oxygen deprivation. Astrogliosis occurred primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice.

Mentions: Since astrocytes are known to become activated as a response to a variety of CNS pathologies [16] we investigated a possible influence of MCP-1 on the reactive astrogliosis 12 and 36 hours after cerebral ischemia. Comparing analyses of GFAP-stained coronal sections showed no differences with respect to immunoreactivity and morphology between both investigated groups and time-points. Activated astrocytes showed the common distribution and activation primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice (Fig.2).


Monocyte chemoattractant protein-1-deficiency impairs the expression of IL-6, IL-1β and G-CSF after transient focal ischemia in mice.

Strecker JK, Minnerup J, Gess B, Ringelstein EB, Schäbitz WR, Schilling M - PLoS ONE (2011)

MCP-1-deficiency has no impact on astrocyte activation.Whole hemisphere GFAP-stained images comparing the activation of astrocytes between wildtype and MCP-1-deficient animals. Analyses showed no differences with respect to immunoreactivity and morphology between wildtype and MCP-1-deficient mice. GFAP staining showed the common distribution and activation of astrocytes reacting to oxygen deprivation. Astrogliosis occurred primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198727&req=5

pone-0025863-g002: MCP-1-deficiency has no impact on astrocyte activation.Whole hemisphere GFAP-stained images comparing the activation of astrocytes between wildtype and MCP-1-deficient animals. Analyses showed no differences with respect to immunoreactivity and morphology between wildtype and MCP-1-deficient mice. GFAP staining showed the common distribution and activation of astrocytes reacting to oxygen deprivation. Astrogliosis occurred primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice.
Mentions: Since astrocytes are known to become activated as a response to a variety of CNS pathologies [16] we investigated a possible influence of MCP-1 on the reactive astrogliosis 12 and 36 hours after cerebral ischemia. Comparing analyses of GFAP-stained coronal sections showed no differences with respect to immunoreactivity and morphology between both investigated groups and time-points. Activated astrocytes showed the common distribution and activation primarily surrounding the infarcted core in both wildtype and MCP-1-deficient mice (Fig.2).

Bottom Line: Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells.Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia.These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Münster, Münster, Germany. strecker.jan@gmx.de

ABSTRACT
Monocyte chemoattractant protein-1 (MCP-1), a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1) performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2) analyzed a possible impact of MCP-1 on astrocyte activation (3) investigated the cellular origin of respective inflammatory cytokines and (4) analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

Show MeSH
Related in: MedlinePlus