Temporal, regional, and cell-specific changes of iNOS expression after intrastriatal microinjection of interferon gamma and bacterial lipopolysaccharide.
[en] Here we study expression of the inducible isoform of nitric oxide synthases after intrastriatal microinjection of interferon-gamma and bacterial lipopolysaccharide in the rat at different time points to detect time- and localisation-dependent changes of iNOS expression. Three different areas in the striatum and the corpus callosum were evaluated. Antibodies against the glial fibrillary acidic protein and the microglia/brain macrophage epitope ED1 were used to detect colocalization of inducible nitric oxide synthase with astrocytes or activated microglia/brain macrophages, respectively. Inducible nitric oxide synthase-positive cells occurred first in intravascular and perivascular cells at 4 h. Perivascular and parenchymal inducible nitric oxide synthase expression increased up to 24 h in the striatum, whereas in the corpus callosum inducible nitric oxide synthase expression was maximal after 16 h. Inducible nitric oxide synthase was still present in perivascular cells 7 days after immunostimulation. At all time points, inducible nitric oxide synthase was predominantly detected in ED1-positive microglia/brain. Nitrotyrosine immunohistochemistry was performed to detect NO-mediated nitration of proteins at all time points. Nitrotyrosine-positive neurons and microglial cells were detected from 24 h until 7 days after immunostimulation and were absent in controls. Detailed knowledge of the changes in the time course and cellular source of inducible nitric oxide synthase expression following brain immunostimulation provide a basis for establishing treatment strategies and windows of therapeutic intervention during neuroinflammation.
Disciplines :
Neurologie
Auteur, co-auteur :
HENEKA, Michael ; Department of Neurology, University of Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany. m.heneka@uni-bonn.de
Dumitrescu, Lucia; Department of Neurology, University of Bonn, 53105 Bonn, Germany
Löschmann, Peter-A.; Department of Neurology, University of Bonn, 53105 Bonn, Germany
Wüllner, Ulrich; Department of Neurology, University of Bonn, 53105 Bonn, Germany
Klockgether, Thomas; Department of Neurology, University of Bonn, 53105 Bonn, Germany
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Temporal, regional, and cell-specific changes of iNOS expression after intrastriatal microinjection of interferon gamma and bacterial lipopolysaccharide.
This study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 400, A8). The authors wish to thank Drs D.L. Feinstein and E. Galea for fruitful discussion and critical reading of the manuscript.
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