Neurodegenerative disease is one of the fastest growing disease areas with the least number of efficacious therapeutics, partly due to a lack of preclinical models of the human brain that translate successfully to human response. Through the use of Organ-on-a-Chip technology, the human Brain-Chip has been established as a model that emulates in vivo-relevant features of neuroinflammation, an important aspect of many neurodegenerative diseases.
In this note, we describe the Brain-Chip, a comprehensive model of the neurovascular unit including a functional blood-brain barrier (BBB). When exposed to the inflammatory cytokine TNF-α, the Brain-Chip reproduces features of neuroinflammation including BBB disruption, increased permeability, and secretion of proinflammatory cytokines. The human Brain-Chip can be applied to model neuroinflammation, helping researchers elucidate mechanisms of neurodegenerative disease, and test candidate therapeutics in a more human relevant manner.
- Can be applied to study mechanisms of neuroinflammation and evaluate anti-inflammatory drug efficacy
- Reproduces key features of neuroinflammation, including cytokine release, barrier damage, and glial activation
- Inflammatory response is reduced in the absence of microglia, demonstrating the cell type’s importance in neuroinflammation
- Co-treatment with anti-inflammatory drug attenuates inflammatory response, demonstrating ability to use the Brain-Chip for efficacy evaluation