Neuroscience Critical Care Research Group, Department of Intensive Care Medicine, CHUV - Lausanne University Hospital, Rue du Bugnon 46, BH 08.623, 1011, Lausanne, Switzerland.
Curr Neurol Neurosci Rep. 2016 Apr;16(4):31. doi: 10.1007/s11910-016-0638-5.
Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.
脑能量功能障碍已成为外伤性脑损伤 (TBI) 预后的一个重要决定因素。许多使用脑微透析、正电子发射断层扫描和颈静脉球血氧饱和度测定法来研究 TBI 患者脑代谢的研究表明，脑细胞的主要能量底物（即葡萄糖）的可用性严重下降。能量功能障碍会引起脑代谢的适应性改变，包括利用大脑固有的替代能源，如乳酸。二十年的实验和人体研究令人信服地表明，乳酸是脑代谢的主要参与者。谷氨酸诱导的糖酵解激活刺激星形胶质细胞中葡萄糖产生乳酸，随后乳酸转移到神经元（星形胶质细胞-神经元乳酸穿梭）。乳酸不仅用作额外的能量底物，而且还作为信号分子和大脑葡萄糖在脑循环中利用的调节剂。在脑损伤的动物模型（例如，TBI、中风）中，补充外源性乳酸可发挥显著的神经保护作用。在这里，我们总结了主要的临床研究，这些研究表明乳酸和 TBI 后脑乳酸代谢的关键作用。我们还回顾了一些初步的干预性研究，这些研究检查了 TBI 患者外源性乳酸补充，发现高渗乳酸输注对受损大脑具有多种有益特性，包括减轻脑水肿、通过“脑葡萄糖节约效应”改善神经能量代谢以及增加脑血流。高渗乳酸代表了一个有前途的治疗研究领域；然而，需要更大的研究来进一步研究作用机制和对结果的影响。
