代谢物
糖酵解
体内
神经保护
缺血
生物化学
新陈代谢
脑缺血
无氧运动
生物
酸中毒
化学
药理学
内科学
内分泌学
医学
生理学
生物技术
作者
Kefan Wu,Yajing Liu,Yuxuan Wang,Jiabao Hou,Meng Jiang,Shaoqin Lei,Bo Zhao,Zhongyuan Xia
出处
期刊:Biomedicines
[Multidisciplinary Digital Publishing Institute]
日期:2025-03-24
卷期号:13 (4): 789-789
标识
DOI:10.3390/biomedicines13040789
摘要
Background/Objectives: Lactate, classically considered a metabolic byproduct of anaerobic glycolysis, is implicated in ischemic acidosis and neuronal injury. The recent evidence highlights its potential role in sustaining metabolic networks and neuroprotection. This study investigates lactate’s compensatory mechanisms in ischemic brain injury by analyzing post-ischemic metabolic enrichments and inter-regional metabolite correlations. Methods: Dynamic metabolic profiling was conducted using 13C-labeled glucose combined with 1H-13C NMR spectroscopy to quantify the metabolite enrichment changes in a murine cerebral ischemia model (n = 8). In vivo validation included intracerebroventricular pH-neutral lactate infusion in ischemic mice to assess the behavioral, electrophysiological, and mitochondrial outcomes. In vitro, HT22 hippocampal neurons underwent oxygen–glucose deprivation (OGD) with pH-controlled lactate supplementation (1 mM), followed by the evaluation of neuronal survival, mitochondrial membrane potential, and glycolytic enzyme expression. Results: NMR spectroscopy revealed a 30–50% reduction in most cerebral metabolites post-ischemia (p < 0.05), while the quantities of lactate and the related three-carbon intermediates remained stable or increased. Correlation analyses demonstrated significantly diminished inter-metabolite coordination post-ischemia, yet lactate and glutamate maintained high metabolic activity levels (r > 0.80, p < 0.01). Lactate exhibited superior cross-regional metabolic mobility compared to those of the other three-carbon intermediates. In vivo, lactate infusion improved the behavioral/electrophysiological outcomes and reduced mitochondrial damage. In the OGD-treated neurons, pH-neutral lactate (7.4) reduced mortality (p < 0.05), preserved the mitochondrial membrane potential (p < 0.05), and downregulated the glycolytic enzymes (HK, PFK, and PKM; p < 0.01), thereby attenuating H+ production. Conclusions: Under ischemic metabolic crisis, lactate and the three-carbon intermediates stabilize as critical substrates, compensating for global metabolite depletion. pH-neutral lactate restores energy flux, modulates the glycolytic pathways, and provides neuroprotection by mitigating acidotoxicity.
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