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Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity

Journal

FLUIDS AND BARRIERS OF THE CNS
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12987-023-00477-6

Keywords

Glycation; Neurovascular unit; Brain; Advanced glycation end-products; Endothelial cells; Astrocytes; Microglia; Pericytes; Vascular smooth muscle cells

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Methylglyoxal (MGO), a by-product of glucose metabolism, negatively impacts the blood-brain barrier (BBB), particularly brain endothelial cells and mural cells. Astrocytes are more resistant to MGO, while microglia produce MGO upon activation. Further research is needed to understand the impact of MGO on the BBB as a multicellular system. Diminishing MGO stress may lead to new treatment strategies for maintaining optimal brain function.
The brain is a highly metabolically active organ requiring a large amount of glucose. Methylglyoxal (MGO), a by-product of glucose metabolism, is known to be involved in microvascular dysfunction and is associated with reduced cognitive function. Maintenance of the blood-brain barrier (BBB) is essential to maintain optimal brain function and a large amount of evidence indicates negative effects of MGO on BBB integrity. In this review, we summarized the current literature on the effect of MGO on the different cell types forming the BBB. BBB damage by MGO most likely occurs in brain endothelial cells and mural cells, while astrocytes are most resistant to MGO. Microglia on the other hand appear to be not directly influenced by MGO but rather produce MGO upon activation. Although there is clear evidence that MGO affects components of the BBB, the impact of MGO on the BBB as a multicellular system warrants further investigation. Diminishing MGO stress can potentially form the basis for new treatment strategies for maintaining optimal brain function.

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