Glucose transport to the brain: a systems model

Abstract

Glucose transport to the brain involves sophisticated interactions of solutes, transporters, enzymes, and cell signaling processes, within an intricate spatial architecture. The dynamics of the transport are influenced by the adaptive nature of the blood-brain barrier (BBB), the semi-impermeable membranes of brain capillaries. As both the gate and the gatekeeper between blood-borne nutrients and brain tissue, the BBB helps govern brain homeostasis. Glucose in the blood must cross the BBB's luminal and abluminal membranes to reach neural tissue. A robust representation of the glucose transport mechanism can highlight a target for brain therapeutic intervention, help characterize mechanisms behind several disease phenotypes, or suggest a new delivery route for drugs. The challenge for researchers is understanding the relationships between influential physiological variables in vivo, and using that knowledge to predict how alterations or interventions affect glucose transport. This paper reviews factors influencing glucose transport and approaches to representing blood-to-brain glucose transport including in vitro, in vivo, and kinetic models. Applications for different models are highlighted, while their limitations in answering arising questions about the human in vivo BBB lead to a discussion of an alternate approach. A developing complex systems simulation is introduced, initiating a single platform to represent the dynamics of glucose transport across the adapting human blood-brain barrier.