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The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

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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 following MCAO. 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.

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Abbreviations

MCAO:

Middle cerebral artery occlusion

IFNγ:

Interferon gamma

OL:

Oligodendrocyte

P3:

Postnatal day 3

E18:

Prenatal day 18

ICA:

Internal carotid artery

ECA:

External carotid artery

rIFNγ:

Recombinant interferon gamma

i.v.:

Intravenous

i.p.:

Intraperitoneal

PBS:

Phosphate buffered saline

DAB:

3 3′-diaminobenzidine

DMSO:

Dimethyl sulfoxide

TBS:

Tris-buffered saline

OGD:

Oxygen glucose deprivation

PDGF-AA:

Platelet derived growth factor-AA

LDH:

Lactate dehydrogenase

MHC:

Major histocompatibility complex

NKT cell:

Natural killer T cell

MPO:

Myeloperoxidase

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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.

Conflicts of Interest

The authors have no conflicts of interest.

Funding

NIH grant RO1 NS052839.

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Authors and Affiliations

  1. Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Hilary A. Seifert, Christopher C. Leonardo, Aaron A. Hall, Derrick D. Rowe, Lisa A. Collier & Keith R. Pennypacker

  2. NeuroScience Associates, Knoxville, TN, 37934, USA

    Stanley A. Benkovic

  3. Center for Excellence in Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Alison E. Willing

Authors
  1. Hilary A. Seifert
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  2. Christopher C. Leonardo
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  3. Aaron A. Hall
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  4. Derrick D. Rowe
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  5. Lisa A. Collier
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  7. Alison E. Willing
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  8. Keith R. Pennypacker
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Correspondence to Keith R. Pennypacker.

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Seifert, H.A., Leonardo, C.C., Hall, A.A. et al. The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling. Metab Brain Dis 27, 131–141 (2012). https://doi.org/10.1007/s11011-012-9283-0

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  • DOI: https://doi.org/10.1007/s11011-012-9283-0

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