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Background : Brain inducible nitric oxide synthase (iNOS) might be detectable in several pathologic conditions, and it is thought to play an important role in their pathophysiology. Tumor necrosis factor (TNF)- and interleukin (IL)-1 are believed to be essential factors of iNOS induction of the brain. Methods : After intrahippocampal stereotaxic injection of lipopolysaccharide (LPS), the rat brains were removed at 6, 12 and 24 h. The rat brain tissues were examined to clarify the expression patterns of TNF- , IL-1 and iNOS. Results : The inflammatory cells which were stained with anti-TNF- antibody, appeared in 6 h and increased for 24 h after LPS injection. The iNOS positive cells appeared after 12 h of LPS injection. A semiquantitative analysis of reverse transcription-polymerase chain reaction (RT-PCR) revealed that the TNF- and IL-1 mRNA arose at 1 h, peaked at 6 h and then declined until 48 h after LPS injection. The iNOS mRNA arose after 6 h, peaked at 12 h, and declined until 48 h after LPS injection. Conclusions : We conclude that the induction of inflammatory events by intrahippocampal injection of LPS activates TNF- and IL-1 secretion, and this is followed by an induction of iNOS expression. TNF- and IL-1 seem to be related with iNOS expression in brain inflammation.

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