Ping Wang1, Jiaqi Zhang2, Feifei Guo1, Shuang Wang2, Yi Zhang1, Defeng Li1, Haiyu Xu3,4, Hongjun Yang5. 1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. 2. Heilongjiang University of Chinese Medicine, Harbin, 150040, China. 3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hy_xu627@163.com. 4. Shaanxi Institute of International Trade & Commerce, Xianyang, 712046, China. hy_xu627@163.com. 5. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hongjun0420@vip.sina.com.
Abstract
BACKGROUND: Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. AIMS: We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). METHODS: We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein-protein interaction (PPI) network construction. RESULTS: Lipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network. CONCLUSIONS: It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.
BACKGROUND:Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. AIMS: We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). METHODS: We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein-protein interaction (PPI) network construction. RESULTS:Lipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network. CONCLUSIONS: It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.
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