Peter Galie, Ph.D.
College of Engineering
The effect of Hemodynamics on the Integrity of the Blood Brain Barrier
Reduced integrity of the blood brain barrier is associated with a wide range of neurological pathologies including traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and dementia. Studying the role of blood flow and vessel stretch in maintaining the blood brain barrier is difficult in animal models due to the complicated hemodynamics in vivo. Our lab has developed a fully three-dimensional, in vitro model of the neurovascular unit that includes cerebral microvasculature endothelial cells, a robust basement membrane, and interaction with astrocytes seeded within the surrounding collagen-hyaluronic acid composite hydrogel. Confocal microscopy demonstrates a functional lumen within these vessels, co-localization of ZO-1 (a scaffold protein associated with the blood brain barrier) to the cell-cell junctions between endothelial cells, as well as astrocyte engagement with the vessel. Preliminary permeability experiments further demonstrate the barrier function of our model using 4 kDa dextran, and the ability to breakdown the barrier through the use of the inflammatory cytokine, TNF-α. Through the use of pulsatile flow, we demonstrate the ability to cyclically stretch the vessel with varying magnitudes and frequencies. Overall, our findings indicate that fluid shear stress is an important regulator of blood brain barrier formation and function.