Development of an in vitro BBB model to study the passage of magnesium taurate and related molecules in the brain compartment

Magnesium and taurine play crucial roles in brain health. On one hand, magnesium plays a role in the synaptic plasticity of neurons, regulating metabolism and harmonizing the transmission of nerve signals. Magnesium depletion causes low-level inflammation, which contributes to neurodegenerative diseases. On the other hand, taurine modulates homeostasis, and neuronal activity, and has neuroprotective capacities. In this context, numerous magnesium vectors have been developed in recent years. Among others, acetylated forms are expected to confer greater lipophilicity and permeability. The aim of the present study is to compare the permeability of these related compounds across the blood-brain barrier (BBB).

First, an in vitro BBB model was developed using a human Brain Microvascular Endothelial Cell (hBMEC) line seeded on Transwell-like cell culture inserts. The passage of the analytes was measured from the upper to the lower chamber of the inserts before, during, and 24 hours after model exposure. A permeability QC was developed to assess representative model permeability using Lucifer Yellow, a fluorescent lipophilic molecule. The permeability of each insert was assessed before and after each test to ensure the integrity of the cells and their tight junctions. Next, the passage of taurine and related compounds was evaluated by an UHPLC (HILIC) MS/MS method, and the passage of magnesium ions was evaluated by ICP MS/MS. Both methods and their sample preparation procedures were carefully optimized to handle the complex culture medium.