<p>Cerebral collateral assessment has become a common metric for treatment planning in acute ischemic stroke patients due to clinical evidence that well-developed collateral networks are correlated with favorable patient outcomes for reperfusion therapies, such as intravenous thrombolytics and mechanical thrombectomy. However, the mechanisms driving these outcome disparities are not well clarified. In the present study, a computational model is used to help clarify these mechanisms by assessing the Circle of Willis hemodynamics during middle cerebral artery occlusion with different levels of collateral development present. The results showed that middle cerebral artery occlusion causes up to a 30% increase in systemic mean arterial pressure, but the increase is less severe in cases with better collateralization, and cases with well-developed collaterals had up to a 66% lower pressure drop across the clot compared to the cases with poor collateral development. The ipsilateral collateral flow increased up to 20-fold following occlusion, which elevated blood flow and mixing distal to the occlusion. These results indicate that cerebral collaterals serve multiple functions that are important to consider in stroke cases. First, collaterals compensate for part of the lost blood flow to the affected brain region by permitting retrograde flow toward the distal end of the occluded vessel. Second, collaterals reduce the pressure forces on the clot, which can improve the susceptibility to reperfusion therapies. Overall, this study shows that we can leverage our unique computational model to better understand the importance of cerebral collateral circulation during stroke and the influence of collaterals on therapeutic outcomes.</p>