Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Römer, C; Engel, O; Winek, K; Hochmeister, S; Zhang, T; Royl, G; Klehmet, J; Dirnagl, U; Meisel, C; Meisel, A.
Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke.
J Neurosci. 2015; 35(20):7777-7794
Doi: 10.1523/JNEUROSCI.1532-14.2015
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- Co-Autor*innen der Med Uni Graz
- Hochmeister Sonja
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- Abstract:
- Stroke-induced immunodepression (SIDS) is an essential cause of poststroke infections. Pharmacological inhibition of SIDS appears promising in preventing life-threatening infections in stroke patients. However, SIDS might represent an adaptive mechanism preventing autoreactive immune responses after stroke. To address this, we used myelin oligodendrocyte glycoprotein (MOG) T-cell receptor transgenic (2D2) mice where >80% of peripheral CD4(+) T cells express a functional receptor for MOG. We investigated in a murine model of middle cerebral artery occlusion the effect of blocking SIDS by inhibiting body's main stress axes, the sympathetic nervous system (SNS) with propranolol and the hypothalamic-pituitary-adrenal axis (HPA) with mifepristone. Blockade of both stress axes robustly reduced infarct volumes, decreased infection rate, and increased long-term survival of 2D2 and C57BL/6J wild-type mice. Despite these protective effects, blockade of SIDS increased CNS antigen-specific Type1 T helper cell (Th1) responses in the brains of 2D2 mice 14 d after middle cerebral artery occlusion. One month after experimental stroke, 2D2 mice developed signs of polyradiculitis, which were diminished by SIDS blockade. Adoptive transfer of CD4(+) T cells, isolated from 2D2 mice, into lymphocyte-deficient Rag-1KO mice did not reveal differences between SIDS blockade and vehicle treatment in functional long-term outcome after stroke. In conclusion, inhibiting SIDS by pharmacological blockade of body's stress axes increases autoreactive CNS antigen-specific T-cell responses in the brain but does not worsen functional long-term outcome after experimental stroke, even in a mouse model where CNS antigen-specific autoreactive T-cell responses are boosted. Copyright © 2015 the authors 0270-6474/15/357777-18$15.00/0.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Autoimmunity -
- CD4-Positive T-Lymphocytes - immunology
- Encephalomyelitis, Autoimmune, Experimental - immunology
- Encephalomyelitis, Autoimmune, Experimental - physiopathology
- Female -
- Homeodomain Proteins - genetics
- Homeodomain Proteins - metabolism
- Infarction, Middle Cerebral Artery - immunology
- Infarction, Middle Cerebral Artery - physiopathology
- Mice -
- Mice, Inbred C57BL -
- Myelin-Oligodendrocyte Glycoprotein - metabolism
- Receptors, Antigen, T-Cell - genetics
- Receptors, Antigen, T-Cell - metabolism
- Th1 Cells - immunology
- Th1 Cells - metabolism
- Find related publications in this database (Keywords)
- CNS autoreactivity
- immunosuppression
- mifepristone
- murine stroke
- propranolol
- stroke-induced immunodeficiency syndrome