Nordström Carl-Henrik, Forsse Axel, Jakobsen Rasmus Peter, Mölström Simon, Nielsen Troels Halfeldt, Toft Palle, Ungerstedt Urban
Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark.
Front Neurol. 2022 Aug 10;13:968288. doi: 10.3389/fneur.2022.968288. eCollection 2022.
The microdialysis technique was initially developed for monitoring neurotransmitters in animals. In 1995 the technique was adopted to clinical use and bedside enzymatic analysis of glucose, pyruvate, lactate, glutamate and glycerol. Under clinical conditions microdialysis has also been used for studying cytokines, protein biomarkers, multiplex proteomic and metabolomic analyses as well as for pharmacokinetic studies and evaluation of blood-brain barrier function. This review focuses on the variables directly related to cerebral energy metabolism and the possibilities and limitations of microdialysis during routine neurosurgical and general intensive care. Our knowledge of cerebral energy metabolism is to a large extent based on animal experiments performed more than 40 years ago. However, the different biochemical information obtained from various techniques should be recognized. The basic animal studies analyzed brain tissue homogenates while the microdialysis technique reflects the variables in a narrow zone of interstitial fluid surrounding the probe. Besides the difference of the volume investigated, the levels of the biochemical variables differ in different compartments. During bedside microdialysis cerebral energy metabolism is primarily reflected in measured levels of glucose, lactate and pyruvate and the lactate to pyruvate (LP) ratio. The LP ratio reflects cytoplasmatic redox-state which increases instantaneously during insufficient aerobic energy metabolism. Cerebral ischemia is characterized by a marked increase in intracerebral LP ratio at simultaneous decreases in intracerebral levels of pyruvate and glucose. Mitochondrial dysfunction is characterized by a moderate increase in LP ratio at a very marked increase in cerebral lactate and normal or elevated levels of pyruvate and glucose. The patterns are of importance in particular for interpretations in transient cerebral ischemia. A new technique for evaluating global cerebral energy metabolism by microdialysis of the draining cerebral venous blood is discussed. In experimental studies it has been shown that pronounced global cerebral ischemia is reflected in venous cerebral blood. Jugular bulb microdialysis has been investigated in patients suffering from subarachnoid hemorrhage, during cardiopulmonary bypass and resuscitation after out of hospital cardiac arrest. Preliminary results indicate that the new technique may give valuable information of cerebral energy metabolism in clinical conditions when insertion of an intracerebral catheter is contraindicated.
微透析技术最初是为监测动物体内的神经递质而开发的。1995年，该技术被应用于临床，用于床边葡萄糖、丙酮酸、乳酸、谷氨酸和甘油的酶分析。在临床条件下，微透析还被用于研究细胞因子、蛋白质生物标志物、多重蛋白质组学和代谢组学分析，以及药代动力学研究和血脑屏障功能评估。本综述重点关注与脑能量代谢直接相关的变量，以及常规神经外科手术和普通重症监护期间微透析的可能性和局限性。我们对脑能量代谢的认识在很大程度上基于40多年前进行的动物实验。然而，应该认识到从各种技术获得的不同生化信息。基础动物研究分析的是脑组织匀浆，而微透析技术反映的是探针周围狭窄间质液区域中的变量。除了所研究体积的差异外，不同隔室中生化变量的水平也不同。在床边微透析期间，脑能量代谢主要反映在测得的葡萄糖、乳酸和丙酮酸水平以及乳酸与丙酮酸（LP）比值上。LP比值反映细胞质氧化还原状态，在有氧能量代谢不足时会立即升高。脑缺血的特征是脑内LP比值显著升高，同时脑内丙酮酸和葡萄糖水平降低。线粒体功能障碍的特征是LP比值适度升高，同时脑乳酸显著升高，丙酮酸和葡萄糖水平正常或升高。这些模式对于短暂性脑缺血的解释尤为重要。讨论了一种通过对引流的脑静脉血进行微透析来评估全脑能量代谢的新技术。在实验研究中已表明，明显的全脑缺血反映在脑静脉血中。已对蛛网膜下腔出血患者、体外循环期间以及院外心脏骤停复苏后的患者进行了颈静脉球微透析研究。初步结果表明，当禁忌插入脑内导管时，这项新技术可能会在临床条件下提供有关脑能量代谢的有价值信息。
