Figure 1

Microphysiological model of the neurovascular unit that supports blood, brain, and cerebral spinal fluid compartments. The system, under development by Vanderbilt University, Meharry Medical College, and the Cleveland Clinic Foundation, utilizes two rectangular, microfabricated compartments representing the brain and the cerebral spinal fluid (CSF) that are separated by a planar ependymal layer that forms the brain-CSF barrier. The upper chamber contains the neurons (purple and blue) and an artificial, hollow fiber (HF) capillary that carries blood to the brain surrounded by the cells that make up the blood-brain barrier (BBB). Endothelial cells line the luminal surface of the HF, and astrocytes (pink) and pericytes (green) cover the abluminal surface. The lower chamber is filled with CSF and contains a small HF that serves as an artificial choroid plexus (red) that produces CSF, and a larger HF venule (blue) that carries blood away from the brain and controls entry of immune cells into the CSF. Each HF, with inner diameters ranging from 200 to 600 μm, is lined with endothelial cells and surrounded by the appropriate cells for choroid plexus and venule function. The lower compartment thereby supports a collection of cells that form the blood-CSF and CSF-brain barriers. Collectively, all the cells will reproduce the neurovascular microenvironment found in the brain. Leukocytes can circulate in the blood-surrogate medium. Microdialysis fibers (not shown) in each compartment will enable near-real-time monitoring of metabolites and signaling molecules. The geometry is suitable for massive parallelization as required for high-content screening, and for daisy-chaining different brain regions to allow the study, for example, of chemical communication in the developing brain.