Lipopolysaccharide-based endotoxemia produce toxicity in peripheral organs and microglia migration in a dose-dependent manner in rat substantia nigra

Abstract

The peripheral inflammatory stimulus could induce cell damage in peripheral organs and activate microglial cells in the brain. One such stimulus was given to adult male Wistar rats by injecting different concentrations of lipopolysaccharide (LPS; 50, 300, 500 μg/kg and 5 mg/kg i.p.). To verify the systemic effect of the LPS administration, the serum content of C-reactive protein (CRP), the variation of body weight and cellular changes in the spleen, liver and kidney were determined. Motor impairment was evaluated by rotarod and open field tests. Microglia activation and dopaminergic degeneration was confirmed by immunolabelling for CD11b/c (microglia) and tyrosine hydroxylase (TH), respectively. The cell counting was performed in substantia nigra pars compacta (SNpc), microglial activation was explored in SNpc, substantia nigra pars reticulata (SNpr), substantia nigra pars compacta dorsal (SNcd) and the ventral tegmental area (VTA). For the statistical analysis, one-way ANOVA followed by Tukey post hoc test (p ≤ 0.05) was used. On day 7 post intraperitoneal administration of LPS, cellular atrophy was detected in the liver, kidney and spleen at 5 mg/kg, without significant changes in CRP levels. Body weight loss and motor impairment was present only on day 1 post LPS administration. The dosage of 500 μg/kg and 5 mg/kg of LPS caused the loss of dopaminergic neurons (40%) in SNpc and microglia migration in a dose-dependent manner in SNcd, SNpc and SNpr. LPS-induced endotoxemia favours damage to the peripheral organs and microglial migration in a dose-dependent manner in rat substantia nigra.

Does lipopolysaccharide-based neuroinflammation induce microglia polarization?

“…Furthermore, depending on the LPS that is injected in SN [24,78], globus pallidus [102], neostriatum [19] or lateral ventricles [43], the microglial activation is indistinctly characterized by morphological changes, cellular stress and antiand pro-inflammatory cytokine production. On the contrary, the intraperitoneal injection of LPS in adult rats (LPS-induced endotoxemia) causes microglia migration (and priming) in a dose-dependent manner in substantia nigra (pars compacta, compacta dorsal and pars reticulata) and damage in peripheral organs [10,13,17,87]; while in mice the chronic LPS administration induces motor deficits caused by alterations in the dopaminergic neurons of SN [16,50,65], and cellular stress in organs [72]. In addition, LPS promotes loss of dopaminergic neurons of neonatal rats when their mothers receive the intraperitoneal administration of this immunogen on day 9.5 [39] or 10.5 prenatal [110].…”