脑损伤

    Involvement of glucose transporter overexpression in the protection or damage after ischemic stroke
  • Figure 1|Adaptive metabolic response in cerebral ischemic conditions.

    Beneficial effects of up-regulation of glucose transporters: Within the central nervous system, susceptibility to ischemia varies among different cell types, with astrocytes and vascular endothelial cells being more capable of withstanding ischemic conditions than neurons and oligodendrocytes. In the course of ischemia, the brain’s glucose uptake and glycolysis show an increasing trend, along with the conversion of higher levels of glucose-6-phosphate, fructose-6-phosphate, pyruvate, and lactate (Geng et al., 2019). This response is partially associated with a significant up-regulation of the glucose transporters expression trying to cover the neuronal energy demand. Models of oxygen and glucose deprivation show that signaling pathways that increase the expression of the GLUT1 are activated to optimize glucose uptake from the bloodstream in the cerebral vascular endothelial cells (Figure 1). Additionally, glycogen is immediately converted to lactate in astrocytes, from where it is released to the interstitium and taken up by neurons, ensuring, at least temporarily, their function. In addition to this response, there is an increase in GLUT1 expression that improves glucose uptake and restores the intracellular glycogen stores in astrocytes located at the penumbra. Interestingly, neurons and astrocytes also respond by up-regulating GLUT3 expression and promoting its translocation towards the cell membrane. Glutamate excitotoxicity induces this response in vitro (primary cerebellar granular neurons) and in vivo middle cerebral artery occlusion models of ischemia (Gutiérrez Aguilar et al., 2020, Koepsell, 2020). Significantly, ischemic preconditioning (exposure to multiple mild ischemic stimuli previous to exposure to prolonged severe ischemia) induces the overexpression of both GLUT1 and GLUT3 in astrocytes and neurons eliciting a neuroprotective effect. Additionally, hyperglycemia up-regulates GLUT3 mRNA expression and GLUT3 protein synthesis and improves cerebral recovery during hypoxia-ischemia in neonatal rats. Similarly, GLUT1 up-regulation in cells from diabetic rats attenuates the exacerbation of cerebral ischemic injury induced by this disease (Iwata et al., 2014). 


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  • 发布日期: 2021-10-18  浏览: 535
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