The role of oxygen in cerebrovascular control: a mathematical analysis

A former model of cerebrovascular regulation and intracranial pressure dynamics has been improved to account for the effect of oxygen lack on cerebral vessels and cerebral blood flow (CBF). The model assumes that CBF regulation is the result of three distinct feedback mechanisms working on pial arteries and arterioles: they represent CO₂ reactivity, tissue hypoxia, and a mechanism (either pressure-dependent or flow-dependent in nature) that does not depend on O₂ or CO₂ directly. With a suitable choice of the mechanism gains, assigned by means of an automatic best-fitting procedure, the model is able to reproduce the pattern of inner radii in small and large pial arteries and CBF during hypoxia and hypotension quite well. These results suggest that autoregulation to perfusion pressure changes cannot be explained merely on the basis of tissue hypoxia, but it requires the presence of further flow-dependent response at the level of small arterioles. Finally, model simulations suggest that acute hypoxia, in a patient with reduced cerebrospinal fluid (CSF) outflow, may induce a significant increase in intracranial pressure, with the risk of secondary brain damage. The model may be of value to improve the present understanding of cerebrovascular control in a large range of clinical conditions.