Mechanical constraints with arterial stiffness having impact on neurovascular coupling and microvascular flow regulation

The brain is an energy-starved organ that continuously draws resources from the blood to sustain neuronal activity. This demand varies across regions and changes dynamically as local neural populations require more metabolic support as they fire. The process that regulates blood supply to these shifting energy demands is known as neurovascular coupling (NVC). This coupling is made possible by contractile cells that wrap around blood vessels, finely controlling vascular tone and perfusion. However, both the vessels and the cells that ensheath them are heterogeneously zonated. As vessels branch into smaller diameters, the contractility of mural cells diminishes and their coverage becomes sparser. At the capillary scale, pericytes are thought to regulate local tone and mediate minimal adjustments in blood flow, but their contractile capabililty are hardly noticeable.

Because blood flow is the means by which metabolic energy is delivered, I view NVC as a form of energy distribution across the brain. This led me to two main questions:

(a) How does the mechanical stress to the vasculature set the boundary conditions for neurovascular coupling?
(b) How does the brain preserve NVC with spatial precision in regions that lack sufficient contractile support? Could passive hemodynamics from upstream vessels alone coordinate the redistribution of blood? If so, how do these regions signal their demand to higher-order vessels to dilate and increase cerebral blood flow/volume without excessive delay in the hemodynamic response?

These questions led me to examine the mechanical side of neurovascular control: thinking dynamics of cereberal vessel wall as boundary conditions that shape how neural activity is translated into blood flow. Physiological factors such as arterial stiffness, vascular calcification, or altered shear stress can change the compliance of vessels and distort local hemodynamic responses. In particular, I was interested in how vascular calcification contributes to arterial stiffening and disrupts the normal buffering of pulsatile pressure. When the vessel wall loses its elasticity, the balance of hemodynamic forces becomes dysregulated. Over time, this imbalance further damages the endothelium, accelerates mechanical fatigue, and amplifies calcification, forming a vicious cycle of stiffness and stress.

This project was originally designed as an in-vivo study using two-photon calcium imaging in transgenic mice to longitudinally observe how arterial stiffness alters neurovascular dynamics. The experiment involved microsurgical induction of carotid calcification to model chronic vascular stiffening. However, after developing a severe allergic and ultimately anaphylactic reaction to mice, I had to discontinue the animal work. Although it was an unexpected setback, it became a turning point in my research path. After this event, I shifted towards to human neuroimaging and computational modeling and study brain-wide networks and dynamic systems.