Expression Changes in Lactate and Glucose Metabolism and Associated Transporters in Basal Ganglia following Hypoxic-Ischemic Reperfusion Injury in Piglets.

Abstract

The neonatal brain has active energy metabolism, and glucose oxidation is the major energy source of brain tissue. Lactate is produced by astrocytes and released to neurons. In the central nervous system, lactate is transported between neurons and astrocytes via the astrocyte-neuron lactate shuttle. The aim of this study was to investigate the regulatory mechanisms of energy metabolism in neurons and astrocytes in the basal ganglia of a neonatal hypoxic-ischemic brain injury piglet model. A total of 35 healthy piglets (3-5 days of age; 1.0-1.5 kg) were assigned to a control group (n = 5) or a hypoxic-ischemic model group (n = 30). The hypoxic-ischemic model group was further divided into 6 groups according to the 1H-MR spectroscopy and PET/CT scan times after hypoxia-ischemia (0-2, 2-6, 6-12, 12-24, 24-48, and 48-72 hours; n = 5/group). 1H-MR spectroscopy data were processed with LCModel software. Maximum standard uptake values refer to the maximum standard uptake values for glucose (or FDG). The maximum standard uptake values of the basal ganglia-to-occipital cortex ratio were analyzed. The expression levels of glucose transporters and monocarboxylate transporters were detected by immunohistochemical analysis. Lactate levels decreased after an initial increase, with the maximal level occurring around 2-6 hours following hypoxia-ischemia. After hypoxia-ischemia, the maximum standard uptake values of the basal ganglia and basal ganglia/occipital cortex initially increased then decreased, with the maximum occurring at approximately 6-12 hours. The lactate and glucose uptake (basal ganglia/occipital cortex maximum standard uptake values) levels were positively correlated. The expression levels of glucose transporter-1 and glucose transporter-3 were positively correlated with the basal ganglia/occipital cortex. The expression levels of monocarboxylic acid transporter-2 and monocarboxylic acid transporter-4 were positively correlated with lactate content. The results indicate that lactate and glucose transporters have a synergistic effect on the energy metabolism of neurons and astrocytes following hypoxic-ischemic reperfusion brain injury.