Cardiac arrest is one of the major causes of death and disability. The aim of the study was to identify dynamic time-dependent metabolomic changes reflected in rat plasma induced by cerebral ischemia and reperfusion with the focus on the protective effect of ischemic preconditionig. Global cerebral ischemia in rats was induced by the four-vessel occlusion. Blood plasma was collected in three reperfusion times: an early post-acute 3 hr, then 24 hr, as an incipient time for delayed neuronal death induction and 72 hr as prolonged reperfusion period. The metabolomic measurements were conducted via untargeted nuclear magnetic resonance spectroscopy. Plasma of ischemized rats manifested dynamic metabolomic changes over the reperfusion time, such as increased levels of ketone bodies, decreased levels of pyruvate, alanine, and citrate. All three branched chain amino acids showed common pattern during reperfusion time: a decrease in 3 hr compared to sham, then a highest level in 24 hr and decrease in 72 hr reperfusion time, similar to their corresponding ketoacids. The protective effect of ischemic preconditioning was demonstrated by a faster tendency of plasma metabolites to normalize. Results also proved the remarkable metabolomic differences between the control (naïve) and sham-operated anesthetized animals, what warrants for critical evaluation of surgery/anaesthesy in the algorithm of metabolomic animal studies.

中文翻译：

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大鼠全脑缺血再灌注后血浆时间相关代谢组学研究：缺血预处理的影响

心脏骤停是导致死亡和残疾的主要原因之一。该研究的目的是确定脑缺血和再灌注诱导的大鼠血浆中反映的动态时间依赖性代谢组学变化，重点是缺血预处理的保护作用。四血管闭塞诱发大鼠全脑缺血。在三个再灌注时间收集血浆：早期急性后 3 小时，然后是 24 小时，作为延迟神经元死亡诱导的起始时间和 72 小时作为延长的再灌注期。代谢组学测量是通过非靶向核磁共振波谱进行的。缺血大鼠的血浆在再灌注时间内表现出动态代谢组学变化，例如酮体水平增加，丙酮酸、丙氨酸和柠檬酸盐水平降低。所有三种支链氨基酸在再灌注时间都显示出共同的模式：与假手术相比，3 小时内减少，然后在 24 小时内达到最高水平，再灌注时间在 72 小时内减少，类似于它们相应的酮酸。血浆代谢物恢复正常的更快趋势证明了缺血预处理的保护作用。结果还证明了对照（初治）和假手术麻醉动物之间显着的代谢组学差异，这需要在代谢组学动物研究的算法中对手术/麻醉进行严格评估。血浆代谢物恢复正常的更快趋势证明了缺血预处理的保护作用。结果还证明了对照（初治）和假手术麻醉动物之间显着的代谢组学差异，这需要在代谢组学动物研究的算法中对手术/麻醉进行严格评估。血浆代谢物恢复正常的更快趋势证明了缺血预处理的保护作用。结果还证明了对照（初治）和假手术麻醉动物之间显着的代谢组学差异，这需要在代谢组学动物研究的算法中对手术/麻醉进行严格评估。