Computational simulation and modeling of the blood-brain barrier pathology

In silico methods and models in the pathology of the blood-brain barrier (BBB) or also called BBB "computational pathology", are based on using mathematical approaches together with complex, high-dimensional experimental data to evaluate and predict disease-related impacts on the CNS. These computational methods and tools have been designed to deal with BBB-linked neuropathology at the molecular, cellular, tissue, and organ levels. The molecular and cellular levels mainly include molecular docking and molecular dynamics simulations (atomistic and coarse-grain) of mutated or misfolded tight junction proteins, receptors, and various BBB transporters. The tissue and organ levels encompass the mechanistic and pharmacokinetic models as well as finite-element method and pathway analyses enriched with multiple sources of raw data (e.g., in vitro and in vivo, histopathological records, "-omics", and imaging data). Overall, this review discusses comprehensive computational techniques and strategies at different levels of complexity, providing new insights and future directions for diagnosis, treatment improvement, and a deeper understanding of BBB-related neuropathological events.