Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat
Section snippets
Animals and LPS injection
Male Sprague–Dawley rats (175–200 g; Taconic Farms, Germantown, NY) were group housed and handled daily prior to experimentation. They were injected intravenously (i.v.) with different doses (0.01 μg/kg, 0.1 μg/kg, 10 μg/kg, or 1 mg/kg) of LPS (E. Coli, serotype 055:B5, Sigma) dissolved in 0.9% saline or 0.9% sterile saline alone. Animals were then killed by decapitation at 2 and 12 h after the injection (n=4 per group). Injections were timed so that the time of sacrifice fell between 09:00 and
Results
Representative film autoradiographs of IL-1β mRNA hybridization in coronally cut sections at the level of OVLT (Fig. 1, A–C) and SFO (Fig. 1, D–F) are shown in Fig. 1. These sections are collected from animals that were sacrificed at 2 h after LPS injections. No labeling was observed in any sections hybridized with sense probes (same as Fig. 1A and D, data not shown). With antisense probe, dose-dependent IL-1β mRNA hybridization in OVLT and SFO, choroid plexus, and meninges was detected after
Discussion
The results of the present study show that the pro-inflammatory cytokines IL-1β and TNFα are dose-dependently induced in the CVOs, choroid plexus, and meninges by peripherally injected LPS. The threshold dose for the induction of these cytokines by i.v.-injected LPS was 10 μg/kg in the rat. The induction of these cytokines in the above-mentioned brain regions paralleled the induction of c-fos mRNA expression in the PVN and NTS. The mRNA induction of the cytokine-responsive immediate early gene
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