The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling
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.
KeywordsBrain ischemia Cytokine Microglia/macrophages MCAO
Middle cerebral artery occlusion
Postnatal day 3
Prenatal day 18
Internal carotid artery
External carotid artery
Recombinant interferon gamma
Phosphate buffered saline
Oxygen glucose deprivation
Platelet derived growth factor-AA
Major histocompatibility complex
- NKT cell
Natural killer T cell
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.
NIH grant RO1 NS052839.
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