Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

Abstract

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia.

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

“…Several recent MRI studies have all suggested a moderate increase of CMRO 2 due to hypoxia. 2,40,48 In this regard, the observation in the present study is in good agreement with these prior findings. It is still unclear what the physiological mechanism is that could explain the elevated brain oxygen metabolic rate during hypoxic state.…”

“…These values are with the typical range of the literature reports. 1,2,12,18,[35][36][37][38][39][40][41][42] But the effect of gas modulation on neural or metabolic activity is not fully understood and is in fact still controversial. This is primarily due to a lack of tools to examine these questions, because one can no longer use vascular surrogate marker (for which plenty of tools are available) and must use direct assessment of neural activity or metabolic rate.…”

Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

“…S6), including decreased r s a O 2 (79±7% of the baseline value measured under normoxia) and increased rOEF (148±14%), rCBF total (141±40%), and rCMRO 2 (156±21%). These observations in the hypoxic mouse brain nicely echoed a recent human study using magnetic resonance imaging (Vestergaard et al, 2016). …”

Lessons from the laboratory; integrated regulation of cerebral blood flow during hypoxia

“…Cerebral OEF is inversely proportional to CBF when metabolism is held constant, and directly proportional to metabolism when CBF is held constant, consistent with the conservation of (O 2 ) mass principle. The effects of acute hypoxia on CMRO 2 are minimal, with reports of slight (5-8.5%) increases (Xu et al 2012;Vestergaard et al 2015) or no changes (Kety & Schmidt, 1948;Cohen et al 1967;. Differences in measurement techniques and the degree of hypoxia and/or CO 2 control might explain these small differences.…”

“…For example, recent animal studies have reported that brainstem parenchymal P O 2 is ß60 mmHg lower than P aO 2 even during normoxia (Marina et al 2015). At least during periods of acute (40 min) exposure to poikilocapnic hypoxia (fractional inspired O 2 of 0.10), however, a recent human-based magnetic resonance proton spectroscopy study reported small elevations in CBF and CMRO 2 (ß8%) and reductions in creatine and phosphocreatine concentrations of ß15% (Vestergaard et al 2015). The authors speculated that a shift towards creatine-mediated ATP catalysis as a manifestation of hypoxia could reflect a defence mechanism.…”