Authors
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
Published in
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. Pages 271678X261485404. Aug 26, 2026. Epub Aug 26, 2026.
Abstract
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.
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.
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).
LPG calculated per time segment provides a more accurate, outcome-associated proxy for anaerobic activity than datapoint-level LPR.
PMID:
42644382
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.
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