The role of leptomeningeal collaterals in redistributing blood flow during stroke

PLoS Comput Biol. 2023 Oct 23;19(10):e1011496. doi: 10.1371/journal.pcbi.1011496. eCollection 2023 Oct.

Abstract

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.

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain Ischemia*
  • Cerebrovascular Circulation / physiology
  • Mice
  • Stroke*

Grants and funding

RE, FS and PJ received funding from the Swiss National Science Foundation (https://www.snf.ch) (Grant No. 166707) and ETH Zürich (https://ethz.ch). FS received funding from the Swiss National Science Foundation (Grant No. 202192). BW received funding from the Swiss National Science Foundation (Grant No. 310030_182703). SW received funding from the Swiss National Science Foundation (Grant No. 310030_200703). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.