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 h ybridization histochemistry. Lipopolysaccharide (bacterial endotoxin) injec ted acutely into rat striatum induced mRNA expression for inhibitory factor kappa B alpha, interleukin (IL)-1 beta, tumor necrosis facror-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 ve hicle alone were used to control for mechanical effects. Following lipopoly saccharide administration, a wave of mRNA induction within brain parenchyma radiated outward from the injection site, generally peaking in intensity a t the 16-h time point. The individual profiles of cytokine mRNA induction p atterns reveal that the brain's immune response to local inflammatory stimu lation is quite elaborate and in many ways resembles the progression of cyt okine induction customary of localized inflammation in peripheral tissues. (C) 2000 Elsevier Science B.V. All rights reserved.