The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

Hilary A. Seifert; Christopher C. Leonardo; Aaron A. Hall; Derrick D. Rowe; Lisa A. Collier; Stanley A. Benkovic; Alison E. Willing; Keith R. Pennypacker

doi:10.1007/s11011-012-9283-0

The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

Hilary A. Seifert, Christopher C. Leonardo, Aaron A. Hall, Derrick D. Rowe, Lisa A. Collier, Stanley A. Benkovic, Alison E. Willing, Keith R. Pennypacker

Research output: Contribution to journal › Review article › peer-review

94 Scopus citations

Abstract

Delayed neuronal death associated with stroke has been increasingly linked to the immune response to the injury. Splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective and significantly reduces neuroinflammation. The present study investigated whether splenic signaling occurs through interferon gamma (IFNγ). IFNγ was elevated early in spleens but later in the brains of rats followingMCAO. Splenectomy decreased the amount of IFNγ in the infarct post-MCAO. Systemic administration of recombinant IFNγ abolished the protective effects of splenectomy with a concurrent increase in INFγ expression in the brain. These results suggest a role for spleen-derived IFNγ in stroke pathology.

Original language	English
Pages (from-to)	131-141
Number of pages	11
Journal	Metabolic Brain Disease
Volume	27
Issue number	2
DOIs	https://doi.org/10.1007/s11011-012-9283-0
State	Published - Jun 2012

Bibliographical note

Funding Information:
Acknowledgements We would like to thank Dr. Chris Katnik for his help obtaining neuronal cultures and Dr. Thomas Klein for his insights into immunology. This work was supported by the National Institutes Health grant RO1 NS052839.

Funding Information:
NIH grant RO1 NS052839.

Keywords

Brain ischemia
Cytokine
MCAO
Microglia/macrophages

ASJC Scopus subject areas

Biochemistry
Clinical Neurology
Cellular and Molecular Neuroscience

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10.1007/s11011-012-9283-0

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title = "The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling",

abstract = "Delayed neuronal death associated with stroke has been increasingly linked to the immune response to the injury. Splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective and significantly reduces neuroinflammation. The present study investigated whether splenic signaling occurs through interferon gamma (IFNγ). IFNγ was elevated early in spleens but later in the brains of rats followingMCAO. Splenectomy decreased the amount of IFNγ in the infarct post-MCAO. Systemic administration of recombinant IFNγ abolished the protective effects of splenectomy with a concurrent increase in INFγ expression in the brain. These results suggest a role for spleen-derived IFNγ in stroke pathology.",

keywords = "Brain ischemia, Cytokine, MCAO, Microglia/macrophages",

author = "Seifert, {Hilary A.} and Leonardo, {Christopher C.} and Hall, {Aaron A.} and Rowe, {Derrick D.} and Collier, {Lisa A.} and Benkovic, {Stanley A.} and Willing, {Alison E.} and Pennypacker, {Keith R.}",

note = "Funding Information: Acknowledgements We would like to thank Dr. Chris Katnik for his help obtaining neuronal cultures and Dr. Thomas Klein for his insights into immunology. This work was supported by the National Institutes Health grant RO1 NS052839. Funding Information: NIH grant RO1 NS052839.",

year = "2012",

month = jun,

doi = "10.1007/s11011-012-9283-0",

language = "English",

volume = "27",

pages = "131--141",

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T1 - The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

AU - Seifert, Hilary A.

AU - Leonardo, Christopher C.

AU - Hall, Aaron A.

AU - Rowe, Derrick D.

AU - Collier, Lisa A.

AU - Benkovic, Stanley A.

AU - Willing, Alison E.

AU - Pennypacker, Keith R.

N1 - Funding Information: Acknowledgements We would like to thank Dr. Chris Katnik for his help obtaining neuronal cultures and Dr. Thomas Klein for his insights into immunology. This work was supported by the National Institutes Health grant RO1 NS052839. Funding Information: NIH grant RO1 NS052839.

PY - 2012/6

Y1 - 2012/6

N2 - Delayed neuronal death associated with stroke has been increasingly linked to the immune response to the injury. Splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective and significantly reduces neuroinflammation. The present study investigated whether splenic signaling occurs through interferon gamma (IFNγ). IFNγ was elevated early in spleens but later in the brains of rats followingMCAO. Splenectomy decreased the amount of IFNγ in the infarct post-MCAO. Systemic administration of recombinant IFNγ abolished the protective effects of splenectomy with a concurrent increase in INFγ expression in the brain. These results suggest a role for spleen-derived IFNγ in stroke pathology.

AB - Delayed neuronal death associated with stroke has been increasingly linked to the immune response to the injury. Splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective and significantly reduces neuroinflammation. The present study investigated whether splenic signaling occurs through interferon gamma (IFNγ). IFNγ was elevated early in spleens but later in the brains of rats followingMCAO. Splenectomy decreased the amount of IFNγ in the infarct post-MCAO. Systemic administration of recombinant IFNγ abolished the protective effects of splenectomy with a concurrent increase in INFγ expression in the brain. These results suggest a role for spleen-derived IFNγ in stroke pathology.

KW - Brain ischemia

KW - Cytokine

KW - MCAO

KW - Microglia/macrophages

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DO - 10.1007/s11011-012-9283-0

M3 - Review article

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SN - 0885-7490

VL - 27

SP - 131

EP - 141

JO - Metabolic Brain Disease

JF - Metabolic Brain Disease

IS - 2

ER -

The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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