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Metabolic Brain Disease

, Volume 27, Issue 2, pp 131–141 | Cite as

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
Original Paper

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.

Keywords

Brain ischemia Cytokine Microglia/macrophages MCAO 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hilary A. Seifert
    • 1
  • Christopher C. Leonardo
    • 1
  • Aaron A. Hall
    • 1
  • Derrick D. Rowe
    • 1
  • Lisa A. Collier
    • 1
  • Stanley A. Benkovic
    • 2
  • Alison E. Willing
    • 3
  • Keith R. Pennypacker
    • 1
  1. 1.Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, Morsani College of MedicineUniversity of South FloridaTampaUSA
  2. 2.NeuroScience AssociatesKnoxvilleUSA
  3. 3.Center for Excellence in Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of MedicineUniversity of South FloridaTampaUSA

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