The role of leptomeningeal collaterals in redistributing blood flow during stroke.

Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel in silico approach that incorporates case-specific in vivo data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with in vivo data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke. Author summary: Cerebral ischaemic strokes are a leading cause of death and disability worldwide. Among other factors, the outcome of stroke treatment is determined by the existence and extent of collateral flow paths, which sustain residual blood supply to the obstructed brain region. To improve therapeutic strategies and to reduce reperfusion injuries during treatment, an in-depth understanding of the role of collaterals for maintaining blood supply is indispensable. We performed numerical simulations to quantify how leptomeningeal collaterals impact blood flow redistribution in response to middle cerebral artery occlusion. Our studies have the unique feature that they are consistent with the topology of case-specific pial arterial networks from mouse brains and aligned with sparse in vivo blood flow measurements. This allows the valuable joint interpretation of numerical studies and in vivo experiments. We observed that maintaining perfusion to the obstructed region comes at the cost of reduced blood supply in other areas. Moreover, dilation of arterial vessels improved perfusion in the entire vasculature. Importantly, flow changes vary significantly across and even within vessel types, which underlines the benefits of numerical models with single vessel resolution. Taken together, our framework establishes a strong link between experimental and numerical studies necessary to advance our understanding of perfusion changes in response to stroke and after clot removal. [ABSTRACT FROM AUTHOR]