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Dynamic Alterations of Brain Injury, Functional Recovery, and Metabolites Profile after Cerebral Ischemia/Reperfusion in Rats Contributes to Potential Biomarkers

大鼠脑缺血/再灌注后脑损伤、功能恢复和代谢物谱的动态变化有助于潜在的生物标志物

  • 影响因子:2.57
  • DOI:10.1007/s12031-019-01474-x
  • 作者列表:"Cheng, Xiao","Yang, Ying-Lin","Li, Wei-Han","Liu, Man","Zhang, Shan-Shan","Wang, Yue-Hua","Du, Guan-Hua
  • 发表时间:2020-01-06
Abstract

Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.

摘要

脑缺血再灌注 (I/R) 的特点是最初短暂脑缺血,随后再灌注。在脑 I/R 过程中,多种病理生理过程参与脑损伤和功能恢复。脑 I/R 后动态代谢过程的研究较少。本研究观察大鼠脑 I/R 后脑损伤、功能恢复和代谢产物的动态变化,发现潜在的代谢标志物。采用大脑中动脉闭塞 (MCAO) 90 min 建立大鼠脑缺血再灌注模型。脑梗死面积、脑水肿、行为学检测结果显示,脑 I/R 后不同时期脑损伤和功能恢复均有动态变化。进一步分析显示,脑 I/R 第一天脑损伤严重,从脑 I/R 第 7 天开始有明显的功能恢复, 其次是从第 7 天到第 28 天脑损伤加重的趋势。此外,基质辅助激光解吸电离质谱成像分析显示,第 7 天脑 I/R 时 ATP 、葡萄糖和柠檬酸的表达最高, 这表明能量代谢和氧化磷酸化在脑 I/R 过程中起着重要作用。此外,非靶向代谢组学结果显示,异柠檬酸水平、氧戊二酸/谷氨酸比值、与 TCA 循环相关的丙酮酸水平也在脑 I/R 期间的第 7 天最高,提示缺血再灌注后第 7 天的短暂自发恢复可能与该时期脑内氧化磷酸化和能量代谢有关。总之,本研究结果提示部分小分子代谢产物参与了脑 I/R 时的脑损伤和功能恢复,对治疗药物和诊断标志物的开发具有重要意义。

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翻译标题与摘要 下载文献
影响因子:2.57
发表时间:2020-01-06
DOI:10.1007/s12031-019-01474-x
作者列表:["Cheng, Xiao","Yang, Ying-Lin","Li, Wei-Han","Liu, Man","Zhang, Shan-Shan","Wang, Yue-Hua","Du, Guan-Hua"]

METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:2.75
发表时间:2020-01-01
DOI:10.1007/s00702-019-02124-7
作者列表:["Wang, Xiaodong","Shi, Cunxian","Pan, Hongxia","Meng, Xiaowen","Ji, Fuhai"]

METHODS:The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34^+ and VEGF^+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion.

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