Systems biology analysis of vasodynamics in mouse cerebral arterioles during resting state and functional hyperemia

Cerebral hemodynamics is tightly regulated by arteriolar vasodynamics. In this study, a systems biology approach was employed to investigate how the interplay between passive, myogenic, neurogenic, and astrocytic responses shapes arteriolar vasodynamics in small rodents. A model of neurovascular coupling is proposed in which neurons inhibit and dampen the myogenic response to promote vasodilation during activation, and facilitate the myogenic response to promote rapid vasoconstriction immediately post-activation. In this model, inhibition of the myogenic response is mediated by the hyperpolarization of smooth muscle and endothelial cells. Dampening and facilitation of the response are mediated by neuronal production of nitric oxide and release of neuropeptide Y, respectively. We also introduce a model for gliovascular coupling, in which astrocytes periodically inhibit the myogenic response upon detecting an increase in myogenic activity through interactions between their endfeet and arterioles. Our simulations suggest that in the resting state, delays in myogenic autoregulation can intrinsically generate low-frequency (∼0.1 Hz) oscillations in vessel diameter (vasomotion), in the absence of extrinsic neurogenic or systemic rhythmic inputs. In the active state, these oscillations are disrupted by the neurogenic and astrocytic responses. The biophysical model of arteriolar vasodynamics presented in this study lays the foundation for quantitative analysis of cerebral hemodynamics for cerebrovascular health diagnostics and hemodynamic neuroimaging.