Neuroprotective Role of Lactate after Cerebral Ischemia

Abstract

It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L L-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 microL of 100 mmol/L L-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.

Prevention of Acute/Severe Hypoglycemia-Induced Neuron Death by Lactate Administration

“…In addition to astrocyte-derived lactate, Boumezbeur et al (2011) and van Hall et al (2009) proposed that plasma-borne lactate may have an important role in supporting oxidative brain metabolism, suggesting that plasma-borne lactate fuels up to 60% of all cerebral metabolism and tricarboxylic acid (TCA) cycle activity even under normal physiological conditions. Consistent with this lactate-fuel hypothesis, several lines of study have also provided evidence that lactate can support energy metabolism during ischemia, which can rescue neuronal death after ischemia or under conditions of oxygen GD (Berthet et al, 2009). Recently, Rinholm et al (2011) reported that lactate can support axonal function in white matter under conditions of energy deprivation and that exogenous L-lactate can support oligodendrocyte development and myelination.…”

Lactate as an early predictor of psychomotor development in neonates with asphyxia receiving therapeutic hypothermia

“…These young were subsequently found to have significantly smaller lesions in basal ganglia. In cases where the application of lactate was delayed (after 1 h of reperfusion or later) the neuroprotective effect was no longer demonstrated 21 . In human medicine however, there is very little evidence for the relationship between lactate levels and the prognosis of children following trauma.…”

Targeting of multiple metabolites in neural cells monitored by using protein-based carbon nanotubes

“…It has been hypothesized that astrocytes may produce lactate during neuronal activation. Lactate is then oxidized by neurons to yield energy, playing a neuroprotective role after cerebral ischemia [32,33]. According to other authors, oxidation of lactate by neurons would only be possible if the glycolytic consumption of glucose or its transport were inhibited [34].…”