Microvascular disturbances are common during neurological disorders. These disturbances range from single capillary occlusions (microstroke) to the occlusion of a major feeding artery (ischemic stroke). Assessing the impact of such microvascular alterations experimentally is challenging, which poses a challenge to advancing our understanding of disease origins and treatment. Targeted computational model development is a promising tool to close this gap in knowledge. In the context of microstrokes, we use our bi-phasic blood flow model and our model for microvascular oxygen transport to show that microscale alterations matter for mesoscale blood and oxygen supply.  The impact of vascular variability during ischemic stroke is addressed in our unique simulation framework, which directly incorporates structural and functional in vivo data from mouse experiments via inverse modeling. By highlighting the relevance of arterial flow loops during ischemic strokes, we propose that accounting for vascular variability in stroke treatments can be beneficial for stroke outcomes.