EXPRESS: The microdialysis-derived lactate-pyruvate gradient indicates anaerobic activity after brain injury.

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Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-08-26 DOI:10.1177/0271678X261485404

Michael Steven Baker, Joshua M Heihre, Tomasz Benedykt Kuliński, Claudia Ann Smith, Berfin Barlas, Chisomo Zimphango, Ivan Timofeev, Koby Baranes, Keri L H Carpenter, Mark Kotter, Mathew R Guilfoyle, Elham Rostami, Peter Hutchinson, Adel Helmy

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Abstract

Background: Cerebral microdialysis (CMD) after traumatic brain injury (TBI) has focused on lactate/pyruvate ratio (LPR), overlooking lactate-pyruvate gradient (LPG, the linear regression slope within a time segment of CMD datapoints) as a proxy for anaerobic activity.

Methods: We retrospectively applied changepoint detection to the linear lactate-pyruvate relationship (L = mP + b) over time within patients from two independent CMD-monitored TBI cohorts (Cambridge, n = 510; Uppsala, n = 81), estimating per-segment LPG (m) and intercept (b, capturing metabolic variance). In vitro, we tested whether rotenone-induced mitochondrial dysfunction increases LPG in hiPSC-derived neurons, as expected if LPG tracks anaerobic activity.

Results: In the Cambridge cohort, a median of two linear segments were identified per patient (median LPG = 19.83; median b = 0.54 mM). Between segments, LPR tracked LPG with heavy attenuation (β = 0.255). LPG was negatively associated with cerebral microdialysate glucose (p < 0.001) and 6-month GOSE (p = 0.039). Uppsala data confirmed pipeline robustness and replicated the LPG-glucose association (p = 0.022). LPG was higher in rotenone-treated neurons than controls (32.9 vs. 14.2, p < 0.001).

Conclusion: LPG calculated per time segment provides a more accurate, outcome-associated proxy for anaerobic activity than datapoint-level LPR.

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EXPRESS：微透析产生的乳酸-丙酮酸梯度表明脑损伤后无氧活动。

背景：创伤性脑损伤（TBI）后的脑微透析（CMD）主要关注乳酸/丙酮酸比值（LPR），忽略了乳酸-丙酮酸梯度（LPG， CMD数据点时间段内的线性回归斜率）作为厌氧活动的代表。方法：我们回顾性地对来自两个独立的cmd监测TBI队列（剑桥，n = 510；乌普萨拉，n = 81）的患者的线性乳酸-丙酮酸关系（L = mP + b）应用变化点检测，估计每段LPG (m)和截断量（b，捕获代谢方差）。在体外，我们测试了鱼藤酮诱导的线粒体功能障碍是否会增加hipsc来源神经元中的LPG，如果LPG跟踪厌氧活性，就会像预期的那样。结果：在剑桥队列中，每名患者中位数为两个线性节段（中位数LPG = 19.83；中位数b = 0.54 mM）。在段间，LPR跟踪LPG衰减较大（β = 0.255）。LPG与脑微透析液葡萄糖呈负相关（p < 0.001）， 6个月GOSE呈负相关（p = 0.039）。Uppsala数据证实了管道稳健性，并复制了lpg -葡萄糖相关性（p = 0.022）。鱼藤酮处理神经元的LPG高于对照组（32.9比14.2,p < 0.001）。结论：与数据点水平的LPR相比，每个时间段计算的LPG提供了更准确、与结果相关的厌氧活性代理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

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