Temporal, regional, and cell-specific changes of iNOS expression after intrastriatal microinjection of interferon gamma and bacterial lipopolysaccharide

Here we study expression of the inducible isoform of nitric oxide synthases after intrastriatal microinjection of interferon-gamma and bacterial lipop olysaccharide in the rat at different time points to detect time- and local isation-dependent changes of iNOS expression. Three different areas in the striatum and the corpus callosum were evaluated. Antibodies against the gli al fibrillary acidic protein and the microglia/brain macrophage epitope EDI were used to detect colocalisation of inducible nitric oxide synthase with astrocytes or activated microglia/brain macrophages, respectively. Inducib le nitric oxide synthase-positive cells occured first in intravascular and perivascular cells at 4 h. Perivascular and parenchymal inducible nitric ox ide synthase expression increased up to 24 h in the striatum, whereas in th e corpus callosum inducible nitric oxide synthase expression was maximal af ter 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 nit ration of proteins at all time points. Nitrotyrosine-positive neurons and m icroglial cells were detected from 24 h until 7 days after immunostimulatio n and were absent in controls. Detailed knowledge of the changes in the tim e course and cellular source of inducible nitric oxide synthase expression following brain immunostimulation provide a basis for establishing treatmen t strategies and windows of therapeutic intervention during neuroinflammati on. (C) 2000 Elsevier Science B.V. All rights reserved.