Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

Abstract

Purpose To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia. Methods A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge. Results The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333. Conclusions The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia.

Mitochondrial lactate metabolism is involved in antioxidative defense in human astrocytoma cells

“…In the central nervous system (CNS), astrocytes are the main producers of lactate, which can be shuttled to neurons under periods of high energy demand, a theory known as the astrocyte-neuronal lactate shuttle (Pellerin and Magistretti, 1994;Newington et al, 2013). In periods of exercise or hypoxia, lactate concentrations in the blood can increase, allowing for astrocytic uptake (Overgaard et al, 2012;Harris et al, 2013;Newinton et al, 2013). The cell source of lactate in the former would be the muscles, whereas the latter could come from neurons (Malthankar-Phatak et al, 2008).…”

Edited1H magnetic resonance spectroscopy in vivo: Methods and metabolites

“…Its low concentration and the macromolecule signals at 1.24 and 1.43 ppm limit the detection of lactate in typical, healthy brain . Lactate has been measured using MEGA‐PRESS , single and dual BASING , MQF , and polarization transfer . In these editing methods, the editing pulse is applied at 4.1 ppm, and the signal of the 1.33 ppm peak is detected.…”

Improved detection of lactate and β‐hydroxybutyrate using MEGA‐sLASER at 3 T

“…Lactate is the end‐product of anaerobic glycolysis and is present at a concentration of 0.2–1.0 mM in blood and healthy brain tissue under resting conditions . Elevated concentrations in the brain can be observed in various pathologies associated with hypoxia (e.g., ischemic stroke as result of restricted blood flow), increased metabolism (e.g., tumors), after intense anaerobic exercises, due to Lac transport via the blood–brain‐barrier, during visual simulation and finger‐tapping …”

“…years, ketogenic diet and fasting have gained attention as treatment paradigms for a variety of brain pathologies such as tumors, epilepsy or multiple sclerosis. 13,14 The coupling topologies of Lac (AX 3 ) and BHB (ABMX 3 ) are superimposed on the corresponding structural formulas in Figure 1. The strongest resonances characterizing both metabolite spectra are doublets situated at 1.31 ppm (Lac) and 1.19 ppm (BHB), arising from methyl groups that are J-coupled to methine protons resonating at 4.10 ppm (Lac) and 4.13 ppm (BHB) with coupling constants of J Lac = 7 Hz and J BHB = 6.3 Hz, respectively.…”

“…The methine group in BHB is additionally coupled with a methylene group of two inequivalent protons resonating at 2.29 ppm and 2.39 ppm, resulting in a doublet-of-doublets for the methylene group and a complex multiplet for the methine proton. 2 It should be noted that the Lac resonance at 1.31 ppm is overlapping with threonine 2 (AMX 3 ), which has a doublet resonance at 1.32 ppm that is J-coupled (with a coupling constant J Thr = 6.4 Hz) to a methine resonance at 4.25 ppm. Therefore, the distinction of Lac and threonine (Thr) is not feasible with standard difference editing methods but requires dedicated techniques based on RF pulses with very small bandwidths.…”