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Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain.

机译:脂多糖的外周给药诱导大鼠脑中小胶质细胞的活化。

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Using immunocytochemistry with monoclonal antibodies against surface immunomolecules and Griffonia simplicifolia lectin histochemistry, the microglial cell reaction in rat brain was studied after intravenous injection of lipopolysaccharide (LPS). Activation of microglial cells throughout the brain became apparent within hours and peaked at 8-24 h following administration of 1, 2.5 and 5 mg/kg LPS. High doses of LPS (2.5 and 5 mg/kg) induced a morphological transition of resting ramified microglia to round, macrophage-like cells in the anterior hypothalamus, thalamus and the brainstem. After injection of 1 mg/kg LPS, this morphological transition was only detected in the brainstem. Microglial cell reactivity gradually returned to control levels within 7 days after LPS administration. Furthermore, LPS induced enhanced expression of MHC class II by microglial cells. Maximal up-regulation of MHC class II Ia-antigen was found 3 days following injection of LPS, and only a few highly Ia immunoreactive cells were detectable 7 days following injection of LPS. Despite the presence of highly activated microglial cells in the rat brain, no signs of tissue damage were observed at any time point after injection of LPS examined. In addition to the activation of microglial cells, intravenous injection of LPS induced accumulations of macrophages in blood vessels of the choroid plexus and the brain, but no disruption of vessels with subsequent invasion of parenchyma by blood macrophages was detected. Our data demonstrate that a peripheral immune challenge leads to a high and transitory activation of microglial cells in the brain which could possibly contribute to the pathology of infections and septic shock.
机译:使用带有针对表面免疫分子的单克隆抗体的免疫细胞化学和Griffonia simplicifolia lectin的组织化学,在静脉注射脂多糖(LPS)后研究了大鼠脑中的小胶质细胞反应。施用1、2.5和5 mg / kg LPS后,整个大脑中的小胶质细胞活化在数小时内变得明显,并在8-24小时达到峰值。高剂量的脂多糖(2.5和5 mg / kg)诱导了静息的分支小胶质细胞向下丘脑,丘脑和脑干的圆形巨噬细胞样细胞形态转变。注射1 mg / kg LPS后,仅在脑干中检测到这种形态学转变。 LPS给药后7天内,小胶质细胞反应性逐渐恢复至对照水平。此外,LPS诱导小胶质细胞增强MHC II类的表达。注射LPS后3天发现最大的MHC II类Ia抗原上调,而注射LPS 7天后仅可检测到少数高Ia免疫反应性细胞。尽管大鼠脑中存在高度活化的小胶质细胞,但在注射LPS后的任何时间都未观察到组织损伤的迹象。除了激活小胶质细胞外,LPS静脉注射还诱导了巨噬细胞在脉络丛和大脑血管中的积聚,但未检测到血管破裂,随后血液巨噬细胞侵袭了实质。我们的数据表明,外周免疫挑战会导致大脑中小胶质细胞的高度短暂激活,这可能有助于感染和败血性休克的病理。

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