Bacterial lipopolysaccharide model of neuroinflammation-associated neurodegeneration in Wistar rats: A comparison between different durations of lipopolysaccharide induction.

Abstract

Background and aim: Bacterial lipopolysaccharide (LPS)-induced neuroinflammation can be the most dependable animal model for studying neurodegeneration mechanisms driven by systemic inflammation-induced neuroinflammation. Hence, this study aimed to standardize the LPS model of neuroinflammation by comparing the effect of relatively low-dose LPS administered for different durations on the induction of neurodegeneration in Wistar rats.

Materials and methods: Six groups of six adult Wistar rats per group were used in the study. Group 1 was the control group, and the other five were administered single weekly dose of LPS (170 μg/kg) for increasing durations, ranging from 4 weeks to 8 weeks. The study endpoints included behavioral parameters, neuronal assay results, and the expression of microglia and astrocytes in the frontal cortex, dentate gyrus, and hippocampus.

Results: We observed a significant reduction in the number of neurons and an increase in glial cells at 5 weeks of exposure, along with a decline in memory. Thereafter, these changes were gradual until 7 weeks of exposure. However, at 8 weeks of exposure, there was no further statistically significant worsening compared with the group exposed for 7 weeks.

Conclusion: To effectively induce neuroinflammation and cause neuronal damage, a minimum of five weekly LPS administrations at a dose of 170 μg/kg is required. Moreover, our results recommend a maximum of 7 weeks of LPS exposure to create a chronic inflammatory model of neuroinflammation.