Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, North Dakota 58203, USA
J Neuroinflammation. 2012 Nov 7;9:249. doi: 10.1186/1742-2094-9-249.
We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism.
In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16). Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by a Tukey's post hoc tests or using a Student's t test assuming unequal variances when appropriate.
We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system.
These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.
我们发现，在脂多糖诱导的神经炎症大鼠模型中，醋酸盐补充可显著减少神经胶质细胞激活和促炎细胞因子的释放。为了测试醋酸盐补充的抗炎作用是否特定于 TLR4 介导的损伤，我们测量了在很大程度上由 TLR2 型机制介导的伯氏疏螺旋体诱导的神经莱姆病大鼠中神经胶质细胞激活的标志物。
在这项研究中，大鼠在静脉输注伯氏疏螺旋体（B31-MI-16）后发生莱姆神经伯氏疏螺旋体病。通过口服甘油三乙酸酯（6g/kg）诱导醋酸盐补充。使用免疫组织化学、qPCR 和 Western blot 分析来测量细菌侵入大脑、神经胶质细胞激活以及大脑和循环中的白细胞介素 1β 水平。使用单向方差分析（ANOVA） followed by a Tukey's post hoc tests 或使用 Student's t test assuming unequal variances when appropriate 进行统计分析。
我们发现，与对照组相比，醋酸盐补充使免疫组织化学和 Western blot 分析确定的小胶质细胞激活减少了 2 倍。此外，与对照组相比，醋酸盐补充还使促炎细胞因子 IL-1β 的表达减少了 2 倍。另一方面，尽管针对伯氏疏螺旋体的抗原循环水平显著增加且细菌存在于中枢神经系统中，伯氏疏螺旋体的接种对星形胶质细胞激活没有影响，通过免疫细胞化学和 Western blot 分析确定。
这些结果表明小胶质细胞激活是神经莱姆病的一个重要组成部分，醋酸盐补充可能是一种有效的治疗方法，可降低莱姆神经莱姆病的损伤表型和损伤进展。
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