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 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.
authors.affiliation: Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Seifert
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Leonardo
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Hall
authors.forename: Derrick D
authors.initials: DD
authors.lastname: Rowe
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Collier
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Benkovic
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Keith R
authors.initials: KR
authors.lastname: Pennypacker
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D009930:Organic Chemicals; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000378:metabolism / Q000503:physiopathology*; D013156:Splenectomy; D020521:Stroke / Q000503:physiopathology*
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; D011994:Recombinant Proteins; C435731:fluoro jade; D007371:Interferon-gamma