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

Eline Berends, Robert J van Oostenbrugge, Sébastien Foulquier, Casper G Schalkwijk

Journal: Fluids and barriers of the CNS 2023;20(1):75

PMID: 37875994

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Abstract

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.

Address: Department of Internal Medicine, Maastricht University, Universiteitssingel, Maastricht, 50 6229ER, The Netherlands.; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, Maastricht, 6229ER, The Netherlands.; School for Mental Health and Neuroscience (MHeNs), Maastricht University, Universiteitssingel 40, Maastricht, 6229ER, The Netherlands.; Department of Neurology, Maastricht University Medical Centre (MUMC+), P. Debyelaan 25 6202AZ, Maastricht, The Netherlands.; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, Maastricht, 6229ER, The Netherlands. [email protected].; Department of Neurology, Maastricht University Medical Centre (MUMC+), P. Debyelaan 25 6202AZ, Maastricht, The Netherlands. [email protected].; Department of Pharmacology and Toxicology, Maastricht University, Universiteitssingel 50 6229ER, Maastricht, The Netherlands. [email protected].; Department of Internal Medicine, Maastricht University, Universiteitssingel, Maastricht, 50 6229ER, The Netherlands. [email protected].; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, Maastricht, 6229ER, The Netherlands. [email protected].

DOI: 10.1186/s12987-023-00477-6

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MeSH Terms: Blood-Brain Barrier, Endothelial Cells, Pyruvaldehyde, Magnesium Oxide, Brain