The present review discusses the potential role of resveratrol in regulating AMPK activity on brain before, during, or after ischemia and offer suggestions for feasible future studies.

Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation.

Excitatory amino acid transporters (EAATs) expressed in astrocytes remove the glutamate released by neurons in and around the synaptic cleft. In this manner, astrocytes preserve the signaling functions mediated by glutamate on synapses and prevent excitotoxicity. Additionally, EAAT activation stimulates glucose utilization in astrocytes, linking neuronal activity with astrocyte metabolism. In this chapter, we briefly review the characteristics of the EAATs and the glucose transporters (GLUTs) expressed in the brain. Thereafter, we focus on the effect of EAATs activation and its association with glucose utilization in astrocytes, specifically addressing the role played by Na and Ca ions. Next, we analyze evidence that proposes mechanisms by which the activity of GLUTs could be modulated after EAAT activation (e.g., kinases altering GLUTs traffic to cell membrane). Finally, we analyzed the current knowledge on EAAT function during energy deficiency as a possible inducer of GLUT expression to prevent neuronal damage.