Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment.

Because it is the product of glycolysis and main substrate for mitochondrial respiration, lactate is the central metabolic intermediate in cerebral energy substrate delivery. Our recent studies on healthy controls and patients following traumatic brain injury (TBI) using [6,6-2H2]glucose and [3-13C]lactate, along with cerebral blood flow (CBF) and arterial-venous (jugular bulb) difference measurements for oxygen, metabolite levels, isotopic enrichments and 13CO2 show a massive and previously unrecognized mobilization of lactate from corporeal (muscle, skin, and other) glycogen reserves in TBI patients who were studied 5.7 ± 2.2 days after injury at which time brain oxygen consumption and glucose uptake (CMRO2 and CMRgluc, respectively) were depressed. By tracking the incorporation of the 13C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls. Standard of care treatment of TBI patients in state-of-the-art facilities by talented and dedicated heath care professionals reveals presence of a catabolic Body Energy State (BES). Results are interpreted to mean that additional nutritive support is required to fuel the body and brain following TBI. Use of a diagnostic to monitor BES to provide health care professionals with actionable data in providing nutritive formulations to fuel the body and brain and achieve exquisite glycemic control are discussed. In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined. To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

因为乳酸是糖酵解的产物以及线粒体呼吸的主要底物，所以它是脑能量底物输送过程中的核心代谢中间产物。我们近期对健康对照组以及创伤性脑损伤（TBI）患者使用[6,6 - 2H₂]葡萄糖和[3 - 13C]乳酸，并结合脑血流量（CBF）以及动静脉（颈静脉球）氧含量差值测量、代谢物水平、同位素富集度和13CO₂进行的研究表明，在伤后5.7 ± 2.2天接受研究的TBI患者中，来自身体（肌肉、皮肤及其他部位）糖原储备的乳酸出现了大量且此前未被认识到的动员情况，此时脑氧消耗和葡萄糖摄取（分别为CMRO₂和CMRgluc）降低。通过追踪来自乳酸示踪剂的13C的掺入情况，我们发现TBI患者中由乳酸进行的糖异生（GNG）占全身葡萄糖出现率（Ra）的67.1 ± 6.9%，而在健康、营养良好的对照组中该比例为15.2 ± 2.8%（分别为平均值 ± 标准差）。由有才能且敬业的医疗专业人员在先进设施中对TBI患者进行的标准治疗显示存在分解代谢的身体能量状态（BES）。研究结果表明，TBI后身体和大脑需要额外的营养支持。文中还讨论了使用一种诊断方法来监测BES，以便为医疗专业人员提供可操作的数据，从而提供营养配方来为身体和大脑提供能量并实现精确的血糖控制。特别是，对使用无机和有机乳酸盐、酯及其他化合物的优势进行了研究。到目前为止，对肝功能和肾功能完好的脑损伤患者进行的几项研究表明，与葡萄糖 + 胰岛素治疗相比，外源性乳酸输注可使血糖正常。