In Silico Modeling of Blood-Brain Barrier: Agent-Based Simulation of Cerebral Glucose Transport

摘要

We present a hierarchical agent-directed, agent-based model of the blood-brain barrier (BBB) and use it to simulate cerebral glucose transport. The BBB consists of brain capillary endothelial cells that are joined by tight junctions. The contiguous layer of endothelium protects the brain against harmful blood-borne substances, while simultaneously providing a pathway for the transport of metabolically important nutrients. Continuous, facilitated transport of glucose across the BBB is especially important because the brain has a very limited capacity for glucose storage. A detailed understanding of that transport and the BBB, however, remains elusive due to the inherent complexity of the system and its experimental inaccessibility. In recent years computer modeling and simulation techniques have been applied as experimental tools but are mostly limited to numerical simulations or data mining. The agent-oriented BBB model presented here is based on an established software framework for hierarchical, multi-agent simulation. The system model is capable of multi-scale simulations. We simulate BBB glucose transport and compare the results with experimental data from