We develop three new models of neurovascular coupling at each interface of the neurovascular unit. The neurovascular unit comprises neurons, microvessels, and astrocytes, a type of glial cell that mediates neurovascular communication. We first develop a bidirectional dynamical model of an astrocyte that both controls and responds to dilations of an arteriole. The astrocyte induces dilation by releasing potassium near the vessel in response to increased neural activity, a phenomenon known as functional hyperemia. In the reverse direction, the astrocyte responds to the arteriole movement via mechanosensitive ion channels on its membrane which contacts the arteriole wall. We perform several sensitivity studies of the model, employing both global parameter sensitivity analysis using stochastic collocation, and various model sensitivity studies. In the second model, we consider the neuron-vessel interface, where we simulate a small network of cortical interneurons in contact with a dilating vessel. These perivascular interneurons express mechanosensitive pannexin channels that respond to vessel dilations and constrictions. We use our model to explore how changes in the neural network structure affect the function of the neurovascular connectivity. Our third model is a discrete particle model of a multi-layer fiber-reinforced anisotropic arterial wall, which we develop using the Dissipative Particle Dynamics (DPD) method. The model is constructed based on the true microstructure of the wall and provides an accurate description of the biaxial mechanical behavior of arteries, which we validate with experimental results provided by collaborators. In addition, we add an active mechanism to the discrete particle wall in order to model the arteriolar smooth muscle cell contraction in response to changes in internal pressure (causing the arteriole to constrict with rising pressure) as well as extracellular potassium. We combine the DPD model with the dynamical astrocyte model as a bidirectional system: the vessel dilates with astrocytic potassium release, and the adjacent astrocyte reacts to changes in vessel dilation. The DPD arteriole model provides a bridge between neurovascular model and complex blood flow simulations in DPD, in which existing DPD red blood cell models can be leveraged.
Witthoft, Alexandra Elisabeth,
"Models of Neurovascular Coupling in the Brain"
(2015).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z00Z71N9
