Blossom Vandana, Ullal Sheetal Dinkar, Rai Rajalakshmi, Chakraborthi Shrijeet, Kumar Nayanatara Arun, Pai Mangala M, Vadgaonkar Rajanigandha
Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Department of Pharmacology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Vet World. 2024 Nov;17(11):2567-2576. doi: 10.14202/vetworld.2024.2567-2576. Epub 2024 Nov 22.
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.
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.
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.
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.
细菌脂多糖(LPS)诱导的神经炎症可能是研究全身炎症诱导的神经炎症驱动的神经退行性变机制最可靠的动物模型。因此,本研究旨在通过比较不同持续时间给予相对低剂量LPS对Wistar大鼠神经退行性变诱导的影响,来标准化神经炎症的LPS模型。
本研究使用六组,每组六只成年Wistar大鼠。第1组为对照组,其他五组每周单次给予LPS(170μg/kg),持续时间从4周增加到8周。研究终点包括行为参数、神经元检测结果以及额叶皮质、齿状回和海马中微胶质细胞和星形胶质细胞的表达。
我们观察到暴露5周时神经元数量显著减少,胶质细胞增加,同时记忆力下降。此后,这些变化逐渐发展,直至暴露7周。然而,暴露8周时,与暴露7周的组相比,在统计学上没有进一步显著恶化。
为有效诱导神经炎症并造成神经元损伤,需要每周至少五次给予170μg/kg的LPS。此外,我们的结果建议LPS暴露最长7周以建立神经炎症的慢性炎症模型。