Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine, and PET, Copenhagen University Hospital Rigshospitalet, Glostrup 2600, Denmark.
Danish Headache Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Glostrup 2600, Denmark.
Cereb Cortex. 2022 Mar 4;32(6):1295-1306. doi: 10.1093/cercor/bhab294.
Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P < 10-4), whereas the CMRO2 remained unaffected (P > 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}2}$, P < 10-6; isocapnic hypoxia: $0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}{\mathrm{a}}{\mathrm{O}}_2}$, P = 0.003) but was unaffected by CO (P = 0.36). Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation.
人体暴露于中等程度缺氧会导致脑内乳酸生成，即使脑氧代谢率（CMRO2）不受影响也是如此。我们通过测试缺氧感应介导的脑糖酵解上调假说来寻找这种乳酸生成的机制。描述对抗脑缺氧的途径可以帮助我们了解与缺氧相关的脑疾病。共有 65 名受试者参与了这项研究：30 名受试者暴露于低碳酸缺氧，14 名受试者暴露于等碳酸缺氧，21 名受试者暴露于一氧化碳（CO）。使用这种设置，我们检查了乳酸生成是否对动脉氧浓度的整体降低有反应，还是仅对降低的动脉氧分压有反应。我们通过磁共振成像和光谱测量脑血流量（CBF）、CMRO2 和乳酸浓度。正如预期的那样，CBF 增加（P < 10-4），而 CMRO2 在所有组中均保持不变（P > 0.076）。吸入低氧空气的组中乳酸增加（低碳酸缺氧：$0.0136\ \frac{\mathrm{mmol/L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}2}$，P < 10-6；等碳酸缺氧：$0.0142\ \frac{\mathrm{mmol/L}}{\Delta{\mathrm{S}}{\mathrm{a}}{\mathrm{O}}_2}$，P = 0.003），但 CO 无影响（P = 0.36）。乳酸生成与 CMRO2 降低无关。这些结果表明，乳酸生成的机制是通过感应动脉氧分压降低来上调糖酵解。释放的乳酸可能作为一种参与血管扩张的信号分子发挥作用。
