1 Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge , Cambridge, United Kingdom .
2 Department of Chemistry, University of Cambridge , Cambridge, United Kingdom .
J Neurotrauma. 2018 Sep 1;35(17):2025-2035. doi: 10.1089/neu.2017.5459. Epub 2018 May 18.
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-C lactate metabolism in TBI with "normal" control brain and muscle, measuring C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."
创伤性脑损伤 (TBI) 后会出现代谢异常。葡萄糖通常被认为是主要的能量底物，尽管乳酸也可以作为能量来源。我们比较了 TBI 与“正常”对照脑和肌肉中的 3-C 乳酸代谢，通过测量 C-谷氨酰胺的富集来评估三羧酸 (TCA) 循环代谢。在 9 名严重 TBI 患者、5 名非 TBI 脑外科患者和 5 名休息肌肉（非 TBI）患者的脑内插入微透析导管，用 8mmol/L 的 3-C 乳酸钠进行灌注（脑内 24 小时，肌肉内 8 小时）。微透析液分析采用 ISCUS 和核磁共振。在 TBI 中，用 3-C 乳酸灌注，微透析液葡萄糖浓度无显著增加（平均增加 11.9%，p=0.463），乳酸（增加 174%）、丙酮酸（增加 35.8%）和乳酸/丙酮酸比值（增加 101.8%）显著增加（p=0.028）。微透析液 C-谷氨酰胺分数富集（中位数，四分位距）分别为：TBI 为 5.1（0-11.1）%，对照组脑为 5.7（4.6-6.8）%，TBI 为 0（0-5.0）%，对照组脑为 0（0-0）%，TBI 为 2.9（0-5.7）%，对照组脑为 1.8（0-3.4）%。TBI 和对照组脑之间的 C 富集没有统计学差异，表明两者都通过 TCA 循环代谢 3-C 乳酸，而与肌肉不同。一些 TBI 患者的 C-谷氨酰胺富集高于非 TBI 对照组范围，表明乳酸氧化代谢是 TBI 的“紧急选择”。
