Witthoft, Alexandra Elisabeth.
Models of Neurovascular Coupling in the Brain.
Degree: PhD, Biomedical Engineering, 2015, Brown University
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.
Advisors/Committee Members: Karniadakis, George (Director), Vlahovska, Petia (Reader), Moore, Christopher (Reader), Jones, Stephanie (Reader).
Subjects/Keywords: neurovascular coupling
to Zotero / EndNote / Reference
APA (6th Edition):
Witthoft, A. E. (2015). Models of Neurovascular Coupling in the Brain. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419410/
Chicago Manual of Style (16th Edition):
Witthoft, Alexandra Elisabeth. “Models of Neurovascular Coupling in the Brain.” 2015. Doctoral Dissertation, Brown University. Accessed March 20, 2019.
MLA Handbook (7th Edition):
Witthoft, Alexandra Elisabeth. “Models of Neurovascular Coupling in the Brain.” 2015. Web. 20 Mar 2019.
Witthoft AE. Models of Neurovascular Coupling in the Brain. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Mar 20].
Available from: https://repository.library.brown.edu/studio/item/bdr:419410/.
Council of Science Editors:
Witthoft AE. Models of Neurovascular Coupling in the Brain. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419410/