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要旨:
Lactate is a common metabolic product of anaerobic glucose metabolism. It can freely pass the blood brain barrier and it’s known to play also an important role in brain metabolism. We used pharmaco MRI and tested the effect of systemic lactate application on the BOLD signal in primary visual cortex (V1) of anesthetized non-human primates during visual stimulation. We also monitored the pharmacokinetics of the applied lactate in the blood using microdialysis and HPLC (high performance liquid chromatography) coupled to MS/MS (mass spectrometry). The lactate pharmacokinetics allows us to investigate the actual plasma concentrations of lactate, and thus, how this correlates to changes in the BOLD signal.
After lactate infusion of 0.6 mmol/kg, we observed two consistent effects in the BOLD signal: An initial decrease in visually-induced modulation followed by a subsequent positive baseline shift (n = 10, p < 0.05). The plasma lactate levels significantly increased approximately 9 minutes after systemic application and were correlated with the positive baseline shift in the BOLD signal (p < 0.05). This is in line with a lactate-induced increase of CBF in sensory stimulated regions observed in earlier studies. However, the onsets of lactate increases were late - thereby indicating a lactate buffering mechanism. This could be due to an uptake of lactate by erythrocytes buffering lactate until this capacity is saturated, and plasma levels start to rise with some delay. We conclude that the positive baseline shift in the BOLD signal is triggered by a rise in CBF due to increased plasma lactate. Interestingly, during the observed decrease in visual modulation, (though lactate was already being applied), the lactate levels in the blood were still comparable to the pre-injection concentrations (p < 0.05). How this lactate uptake by erythrocytes influences the BOLD signal has to be further investigated. Nonetheless, our results reveal a complex interaction of lactate in the brain which was only detectable by using pharmaco MRI in combination with neurochemical monitoring of lactate.
