Talk: Modelling blood flow and molecular transport in the cerebral microcirculation: impact of capillary occlusions in Alzheimer’s disease
10:30 - 11:30
Institut de Mécanique des Fluides de Toulouse (IMFT), Université de Toulouse, CNRS, INPT, UPS, Toulouse, France
Max-Planck-Institut für Dynamik und Selbstorganisation (MPIDS)
The cerebral microvascular system is central to the delivery and clearance of vital molecules and metabolic wastes to and from brain cells. For this reason, such a system is involved in various pathologies, ranging from stroke to neurodegenerative diseases. It is therefore essential, both from a fundamental and a clinical perspective, to be able to accurately describe the transport mechanisms underlying the brain microvascular system. To help address this need, we develop and validate a computational model that is capable of solving blood flow and molecular transport in large anatomical networks composed of tens of thousand of vessels. We then use our model to study the earliest stage of Alzheimer’s disease (AD), which is associated with a significant cerebral blood flow decrease. In vivo two-photon microscopy of cortical vasculature in AD mice suggests that such a decrease is caused by a small fraction of capillary occlusions.
However, the detailed consequences of this mechanism on transport phenomena at the scale of a microvascular network are not yet fully understood. That is why we numerically study the effects of an increasing percentage of capillary occlusions in mice and humans. We find that the cerebral blood flow and the supply of molecules decrease linearly with no threshold effect in both species. This means that even a small percentage of capillary occlusions yields significant consequences at the scale of a microvascular network. In particular, we find that these occlusions induce a significant decrease in the supply of molecules to brain cells, which could participate, in
the absence of compensatory mechanisms, in the deterioration of the cerebral activity.