The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling

被引:98
作者
Seifert, Hilary A. [1 ]
Leonardo, Christopher C. [1 ]
Hall, Aaron A. [1 ]
Rowe, Derrick D. [1 ]
Collier, Lisa A. [1 ]
Benkovic, Stanley A. [2 ]
Willing, Alison E. [3 ]
Pennypacker, Keith R. [1 ]
机构
[1] Univ S Florida, Morsani Coll Med, Sch Basic Biomed Sci, Dept Mol Pharmacol & Physiol, Tampa, FL 33612 USA
[2] NeuroSci Associates, Knoxville, TN 37934 USA
[3] Univ S Florida, Morsani Coll Med, Dept Neurosurg & Brain Repair, Ctr Excellence Aging & Brain Repair, Tampa, FL 33612 USA
关键词
Brain ischemia; Cytokine; Microglia/macrophages; MCAO; CEREBRAL-ARTERY OCCLUSION; ISCHEMIA-REPERFUSION; FOCAL ISCHEMIA; T-LYMPHOCYTES; FLUORO-JADE; BRAIN; CELLS; ACTIVATION; INJURY; SIZE;
D O I
10.1007/s11011-012-9283-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (IFN gamma). IFN gamma was elevated early in spleens but later in the brains of rats following MCAO. Splenectomy decreased the amount of IFN gamma in the infarct post-MCAO. Systemic administration of recombinant IFN gamma abolished the protective effects of splenectomy with a concurrent increase in INF gamma expression in the brain. These results suggest a role for spleen-derived IFN gamma in stroke pathology.
引用
收藏
页码:131 / 141
页数:11
相关论文
共 37 条
[1]   The spleen contributes to stroke-induced neurodegeneration [J].
Ajmo, Craig T., Jr. ;
Vernon, Dionne O. L. ;
Collier, Lisa ;
Hall, Aaron A. ;
Garbuzova-Davis, Svitlana ;
Willing, Alison ;
Pennypacker, Keith R. .
JOURNAL OF NEUROSCIENCE RESEARCH, 2008, 86 (10) :2227-2234
[2]   Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats [J].
Ajmo, Craig T., Jr. ;
Vernon, Dionne O. L. ;
Collier, Lisa ;
Pennypacker, Keith R. ;
Cuevas, Javier .
CURRENT NEUROVASCULAR RESEARCH, 2006, 3 (02) :89-98
[3]  
Bal-Price A, 2001, J NEUROSCI, V21, P6480
[4]  
BARRES BA, 1993, DEVELOPMENT, V118, P283
[5]   Sensitization to brain antigens after stroke is augmented by lipopolysaccharide [J].
Becker, KJ ;
Kindrick, DL ;
Lester, MP ;
Shea, C ;
Ye, ZC .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2005, 25 (12) :1634-1644
[6]  
Becker KJ, 2011, STROKE
[7]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[8]   Role of IL-1α and IL-1β in ischemic brain damage [J].
Boutin, H ;
LeFeuvre, RA ;
Horai, R ;
Asano, M ;
Iwakura, Y ;
Rothwell, NJ .
JOURNAL OF NEUROSCIENCE, 2001, 21 (15) :5528-5534
[9]   SEMINARS IN MEDICINE OF THE BETH-ISRAEL-HOSPITAL, BOSTON - THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE-MEDIATED INFLAMMATION [J].
CHROUSOS, GP .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (20) :1351-1362
[10]   Temporary focal ischemia in the mouse: Technical aspects and patterns of Fluoro-Jade evident neurodegeneration [J].
Duckworth, EAM ;
Butler, TL ;
De Mesquita, D ;
Collier, SN ;
Collier, L ;
Pennypacker, KR .
BRAIN RESEARCH, 2005, 1042 (01) :29-36