Blood-brain barrier development: Systems modeling and predictive toxicology.

Area of Science:

• Neuroscience
• Toxicology
• Pharmacology

Background:

• The blood-brain barrier (BBB) regulates substance exchange between blood and brain, crucial for neural function.
• BBB development and integrity are vital for normal brain development, and disruption can have significant impacts.
• The neurovascular unit (NVU) comprises cells and vessels critical for BBB function.

Purpose of the Study:

• To review BBB development, NVU microphysiology, and the effects of BBB disruption on brain development.
• To highlight the current state and future needs of in silico and in vitro models for studying the BBB.
• To emphasize the importance of integrated modeling approaches for neurodevelopmental risk assessment.

Main Methods:

• Review of existing literature on BBB development, NVU function, and modeling approaches.
• Discussion of in silico models for predicting drug/chemical passage across the BBB.
• Examination of in vitro platforms (high-throughput screening, microphysiological systems) for profiling interactions and investigating NVU dynamics.

Main Results:

• Current in silico models predict BBB passage, while in vitro platforms offer data on chemical-biological interactions.
• Engineered human cell-based microphysiological systems provide empirical models for NVU function dynamics.
• There is a need for computational models integrating kinetic and dynamic NVU functions across gestation and different scenarios.

Conclusions:

• Integrated computational and experimental models are essential for understanding BBB dynamics and neurodevelopmental impacts.
• Improved modeling will reduce uncertainty in translating in vitro and in silico data for risk assessment.
• These advancements are critical for protecting neurodevelopmental health from chemical exposures.