Rosenzweig Holly L, Lessov Nikola S, Henshall David C, Minami Manabu, Simon Roger P, Stenzel-Poore Mary P
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
Stroke. 2004 Nov;35(11):2576-81. doi: 10.1161/01.STR.0000143450.04438.ae. Epub 2004 Sep 16.
Tolerance to ischemic brain injury is induced by several preconditioning stimuli, including lipopolysaccharide (LPS). A small dose of LPS given systemically confers ischemic protection in the brain, a process that appears to involve activation of an inflammatory response before ischemia. We postulated that LPS preconditioning modulates the cellular inflammatory response after cerebral ischemia, resulting in neuroprotection.
Mice were treated with LPS (0.2 mg/kg) 48 hours before ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride staining. Microglia/macrophage responses after MCAO were assessed by immunofluorescence and flow cytometry. The effect of MCAO on white blood cells in the brain and peripheral circulation was measured by flow cytometry 48 hours after MCAO.
LPS preconditioning induced significant neuroprotection against MCAO. Administration of low-dose LPS before MCAO prevented the cellular inflammatory response in the brain and blood. Specifically, LPS preconditioning suppressed neutrophil infiltration into the brain and microglia/macrophage activation in the ischemic hemisphere, which was paralleled by suppressed monocyte activation in the peripheral blood.
LPS preconditioning induces neuroprotection against ischemic brain injury in a mouse model of stroke. LPS preconditioning suppresses the cellular inflammatory response to ischemia in the brain and circulation. Diminished activation of cellular inflammatory responses that ordinarily exacerbate ischemic injury may contribute to neuroprotection induced by LPS preconditioning.
多种预处理刺激可诱导对缺血性脑损伤的耐受性，包括脂多糖（LPS）。全身给予小剂量LPS可在脑内赋予缺血性保护作用，这一过程似乎涉及缺血前炎症反应的激活。我们推测LPS预处理可调节脑缺血后的细胞炎症反应，从而产生神经保护作用。
在短暂性大脑中动脉闭塞（MCAO）诱导缺血前48小时，用LPS（0.2mg/kg）处理小鼠。通过2,3,5-三苯基四氮唑氯化物染色测量梗死面积。通过免疫荧光和流式细胞术评估MCAO后的小胶质细胞/巨噬细胞反应。在MCAO后48小时，通过流式细胞术测量MCAO对脑内和外周循环中白细胞的影响。
LPS预处理对MCAO诱导了显著的神经保护作用。在MCAO前给予低剂量LPS可预防脑内和血液中的细胞炎症反应。具体而言，LPS预处理抑制了中性粒细胞向脑内的浸润以及缺血半球中小胶质细胞/巨噬细胞的激活，同时外周血中的单核细胞激活也受到抑制。
在小鼠中风模型中，LPS预处理可诱导对缺血性脑损伤的神经保护作用。LPS预处理可抑制脑内和循环中对缺血的细胞炎症反应。通常会加重缺血性损伤的细胞炎症反应激活减弱可能有助于LPS预处理诱导的神经保护作用。
