Microvascular occlusion and associated hyperperfusion following recanalization

Abstract Background and Aims Despite successful recanalization, over half of acute ischemic stroke (AIS) patients with large vessel occlusions experience poor outcome. Incomplete microvascular reperfusion (IMR) may contribute to this. However, its occurrence remains debated, in part due to clinical observations of hyperperfusion after stroke recanalization. The present study investigated IMR by quantifying micro-clot presence and cerebral perfusion in a swine stroke model of ischemia-reperfusion. Methods 23 swine underwent craniotomy and were randomized into 5 groups, defined by 1-, 2-, or 4-hrs occlusion followed by 4-hrs recanalization; 8-hrs occlusion without recanalization (positive control); or sham (negative control). Middle cerebral artery (MCA) occlusion, induced with aneurysm clips, was confirmed using 3D-Digital Subtraction Angiography, which was used to quantify the area at risk (AAR) of infarction, as well as tissue perfusion. Micro-clots were quantified using CD61+ platelet immuno-staining (number/mm2). Results In the MCA occlusion groups, the infarcted hemisphere showed significantly more micro-clots (Fig. 1) compared to the non-infarcted hemisphere (0.33[0.16-0.71] vs 0.07[0.04-0.13], p=0.003). Micro-clots were more abundant in AAR than remote regions (0.30[0.22-1.06] vs 0.16[0.10-0.41], p=0.039), and correlated with ischemia duration (r=0.708, p=0.007). Relative perfusion levels were increased in all ischemia-reperfusion groups (Fig. 2) regardless of ischemia duration. Conclusion Focal cerebral ischemia and reperfusion results in significant micro-clot presence within the AAR and extends into the whole ischemic hemisphere. It correlates with ischemia duration and, importantly, occurs alongside hyperperfusion in this swine model of recanalized AIS, showing that IMR and hyperperfusion can co-exist.Micro Clots Hyperperfusion