Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.Glucose and oxygen-the principal substrates ofbrain energy metabolism-are consumed by that organ at matched rates that ordinarily maintain stable lactate concentrations. Brain lactate elevations due to lack of oxygen or increased energy demand to the degree of status epilepticus are well-known phenomena, and extensive research on them has created a general impression that brain lactate elevation always reflects pathologic conditions. However, several recent reports suggest that brain activity within the physiologic range may cause brain lactate to rise. In an earlier study using nuclear magnetic resonance spectroscopy (MRS) in vivo, we found that lactate rose in posterior cerebral cortex of rabbits when electric shocks were delivered to the optic nerves (1). Ueki et al. (2) demonstrated lactate elevation in rat somatosensory cortex due to forepaw stimulation. In humans studied by positron emission tomography (PET), Fox et al. (3) showed that visual stimulation caused 30-50% increases in blood flow and glucose uptake of visual cortex, whereas oxygen extraction rose no more than 5%. Newly developed MRS techniques permit repeated noninvasive detection of lactate in a few cc of human brain (4-6). We have used such techniques to show that photic stimulation does indeed cause a clear, although transient, elevation of lactate in human visual cortex; a preliminary report has appeared (7).
Previous studies have found that treatment with lithium over a 4-week period may increase the concentration of N-acetyl-aspartate (NAA) in both bipolar patients and controls. In view of other findings indicating that NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. The aim of the present study was to utilize H magnetic resonance spectroscopy ( H MRS) to further examine the effects of both lithium and sodium valproate upon NAA concentrations in treated euthymic bipolar patients. In the first part of the study, healthy controls (n =18) were compared with euthymic bipolar patients (type I and type II) who were taking either lithium (n =14) or sodium valproate (n =11), and NAA : creatine ratios were determined. In the second part, we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n =9) and compared these to age- and sex-matched healthy controls (n =11), and we quantified the exact concentrations of NAA using an external solution. The results from the first part of the study showed that bipolar patients chronically treated with lithium had a significant increase in NAA concentrations but, in contrast, there were no significant increases in the sodium valproate-treated patients compared to controls. The second part of the study also found no effects of sodium valproate on NAA concentrations. These findings are the first to compare NAA concentrations in euthymic bipolar patients being treated with lithium or sodium valproate. The results support suggestions that longer-term administration of lithium to bipolar patients may increase NAA concentrations. However, the study suggests that chronic administration of sodium valproate to patients does not lead to similar changes in NAA concentrations. These findings suggest that sodium valproate and lithium may not share a common mechanism of action in bipolar disorder involving neurotrophic or neuroprotective effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.