Spatiotemporal induction patterns of cytokine and related immune signal molecule mRNAs in response to intrastriatal injection of lipopolysaccharide.
The brain's response to a direct immune challenge was examined by in situ hybridization histochemistry. Lipopolysaccharide (bacterial endotoxin) injected acutely into rat striatum induced mRNA expression for inhibitory factor kappaBalpha, interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, IL-12 p35, inducible nitric oxide synthase, IL-1 receptor antagonist, and the type 1 IL-1 receptor. Expression patterns were evaluated at select time points ranging from 15 min to 3 days post-injection. Rats injected with vehicle alone were used to control for mechanical effects. Following lipopolysaccharide administration, a wave of mRNA induction within brain parenchyma radiated outward from the injection site, generally peaking in intensity at the 16-h time point. The individual profiles of cytokine mRNA induction patterns reveal that the brain's immune response to local inflammatory stimulation is quite elaborate and in many ways resembles the progression of cytokine induction customary of localized inflammation in peripheral tissues.
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Section on Functional Neuroanatomy, National Institute of Mental Health, Building 36, Room 2D15, Bethesda, MD 20892-4070, USA.
Quan
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Proescholdt
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Herkenham
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D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000276:immunology*; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020672:I-kappa B Proteins; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D000072000:NF-KappaB Inhibitor alpha; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D018664:Interleukin-12; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat