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.

中文翻译：

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大鼠脑缺血/再灌注后脑损伤，功能恢复和代谢产物概况的动态变化有助于潜在的生物标志物。

脑缺血-再灌注（I / R）的特征是最初的短暂性脑缺血然后再灌注。脑I / R期间脑损伤和功能恢复涉及各种病理生理过程。关于脑I / R后动态代谢过程的研究很少。本研究旨在观察大鼠脑I / R后脑损伤，功能恢复和代谢产物的动态变化，并发现潜在的代谢标记物。大鼠再灌注后，通过大脑中动脉闭塞（MCAO）建立90分钟的大脑I / R模型。脑梗死面积，脑水肿和行为测试的结果表明，脑缺血再灌注后不同时期，脑损伤发生动态变化，功能恢复。进一步的分析表明，在脑I / R的第一天，脑损伤就很严重，从脑I / R的第7天开始，其功能就得到了明显的恢复，随后从第7天到28天，脑损伤的加剧趋势此外，基质辅助激光解吸电离质谱成像分析显示，在脑I / R的第7天，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中起重要作用。 I / R。此外，非靶向代谢组学结果显示，与脑缺血再灌注相关的异柠檬酸水平，氧戊二酸/谷氨酸比例和丙酮酸水平也在TCA周期的第7天最高，提示缺血再灌注后第7天缺血性脑的瞬时自发恢复可能与该时期脑中的氧化磷酸化和能量代谢有关。总之，研究结果提示一些小分子代谢物参与了脑I / R期间的脑损伤和功能恢复，这对治疗药物和诊断标志物的开发具有重要意义。