The Effect of Pentoxifylline on Passive Avoidance Learning and Expression of Tumor Necrosis Factor-Alpha and Caspase-3 in the Rat Hippocampus Following Lipopolysaccharide-Induced Inflammation.

BACKGROUND

Peripheral inflammation is effective in the development of neurodegenerative diseases. Pentoxifylline (PTX) has an inhibitory effect on inflammatory cytokines; therefore, we aimed to evaluate the effect of PTX on passive avoidance learning and the expression of tumor necrosis factor-alpha (TNF-α) and in the rat hippocampus, following systemic lipopolysaccharide (LPS) injection.

MATERIALS AND METHODS

Male Wistar rats were randomly divided into five groups: control, LPS, and LPS + PTX, receiving doses of 10, 25, and 50 mg/kg of PTX, respectively. The animals received daily injections of PTX (i.p.) 1 week before and 2 weeks after the LPS injection (5 mg/kg; i.p.). Learning and memory were evaluated by passive avoidance learning. Then, the expression of the associated genes was measured in the hippocampus.

RESULTS

The results showed that the peripheral LPS injection had no significant effect on learning and memory. PTX only with a dose of 10 mg/kg shows an improvement ( < 0.05). Results from reverse transcription polymerase chain reaction showed that LPS had no significant effect on the expression of and TNF-α. PTX with a dose of 10 mg/kg decreased the expression in the LPS + PTX group ( < 0.001), but the expression of both genes increased, using other concentrations.

CONCLUSIONS

Findings showed that systemic application of LPS after 2 weeks had no effect on learning and memory and the expression of inflammatory genes in the hippocampus, but PTX led to an increase in the expression of these genes, which could be due to its direct effects or possible exacerbation of LPS effects.