Glycation Increases the Risk of Microbial Traversal through an Endothelial Model of the Human Blood-Brain Barrier after Use of Anesthetics

Abstract

The function of the human blood–brain barrier (BBB), consisting mainly of the basement membrane and microvascular endothelial cells, is to protect the brain and regulate its metabolism. Dysfunction of the BBB can lead to increased permeability, which can be linked with several pathologies, including meningitis, sepsis, and postoperative delirium. Advanced glycation end products (AGE) are non-enzymatic, posttranslational modifications of proteins, which can affect their function. Increased AGE levels are strongly associated with ageing and degenerative diseases including diabetes. Several studies demonstrated that the formation of AGE interfere with the function of the BBB and may change its permeability for soluble compounds. However, it is still unclear whether AGE can facilitate microbial traversal through the BBB and how small compounds including anesthetics modulate this process. Therefore, we developed a cellular model, which allows for the convenient testing of different factors and compounds with a direct correlation to bacterial traversal through the BBB. Our results demonstrate that both glycation and anesthetics interfere with the function of the BBB and promote microbial traversal. Importantly, we also show that the essential nutrient and antioxidant ascorbic acid, commonly known as vitamin C, can reduce the microbial traversal through the BBB and partly reverse the effects of AGE.

ApoA-I Nanoparticles as Curcumin Carriers for Cerebral Endothelial Cells: Improved Cytoprotective Effects against Methylglyoxal

“…MGO also induced reactive oxygen species (ROS) formation [23,24], blood-brain barrier (BBB) hyperpermeability [25,26], chromatin condensation, and ER stress [27,28], as shown in previous studies.…”

“…MGO was cytotoxic (2 mM) in our cerebral endothelial cell model and, previously, was also shown to be cytotoxic in different cell lines including neuroglial cells, HUVECs, and human brain endothelial cells [ 7 , 21 , 22 ]. MGO also induced reactive oxygen species (ROS) formation [ 23 , 24 ], blood–brain barrier (BBB) hyperpermeability [ 25 , 26 ], chromatin condensation, and ER stress [ 27 , 28 ], as shown in previous studies.…”

Disturbance of Key Cellular Subproteomes upon Propofol Treatment Is Associated with Increased Permeability of the Blood-Brain Barrier

“…Before studying the permeability of the BBB after application of propofol, we analyzed the cell viability of THBMEC cells in the presence of propofol with 3 µg/mL, which is a commonly used concentration in surgery, and found that the cell viability was not affected by propofol (data not shown and in [ 22 ]). The effect of propofol on the permeability of THBMECs was further analyzed.…”

“…There exist several studies indicating that anesthesia can affect the BBB. One particular example we previously investigated was the non-volatile anesthetic propofol [ 22 ]. Propofol is a phenolic derivative and is considered one of the more favorable intravenous anesthetics due to its rapid onset of effect, short plasma half-life and its low accumulation in tissues [ 23 ].…”

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“…The blood-brain barrier (BBB) is the endothelial cell layer of the brain that separates the brain from the blood. It regulates the exchange of drug-like compounds between blood and brain 41 . The ability of the identified compounds to permeate through BBB was predicted and the results are illustrated in Table 5.…”