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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Endothelial Energy Metabolism

Glucose is the major source of energy in neurons. Therefore, it is not surprising that glucose transporter-1 (GLUT1) is one of the most abundant proteins and the solute carrier which is most enriched in the BBB [60]. Under hypoxic conditions (such as that provoked by inflammation in MS), GLUT1 expression can increase in a hypoxia-inducible factor 1-alpha (HIF-1)-dependent manner. This may involve prostanoid signals originating from either hypoxic astrocytes [61] or pericytes [62] and may represent a type of metabolic “switch.” Reductions in GLUT1 expression intensify CNS stress and are frequently observed in Alzheimer’s disease (AD) [63]. Decreased GLUT1 expression and function exacerbate neurovascular degeneration in MS, because of disastrous effects on BBB integrity [64]. Several endothelial functions are compromised by defects in energy homeostasis during MS exacerbations including depressed endothelial barrier function, increased endothelial apoptosis, expression of ECAMs, and conversion into a prothrombotic phenotype, all of which increase disease activity.

 
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