ABSTRACT NUMBER: ESOC2026A2052 CEREBRAL VASCULAR DIAMETER AND FLOW IRREGULARITIES DUE TO ISCHEMIC STROKE AFTER MIDDLE CEREBRAL ARTERY OCCLUSION

Abstract Background and aims Acute ischemic stroke is a major cause of death and disability. Despite advancements in reperfusion therapies, lasting alterations in cerebral vasculature can limit recovery. Research has largely focused on microvascular impairment, while changes in the pial arterial network remain underexplored. Methods Using the middle cerebral artery occlusion model and in-vivo microscopy in mice (n=7), we assessed pial vessel dynamics during occlusion, recanalization, and within the critical 24 hours post reperfusion. Vessel diameter, irregularity, resistance, blood flow, and micro-thrombus formation were quantified. Results Results revealed marked vasoconstriction throughout the pial network during occlusion, which persisted after recanalization, with vessel diameters reduced to ~69% of baseline at 24h. Smaller pial vessels (<30μm) reacted differently over time compared to larger vessels, thereby reaching maximum vasoconstriction already at 45min after recanalization. Overall vessel irregularity and resistance increased and peaked at 24 hours. A considerable proportion of vessels had impaired (sluggish and reversed) flow despite successful recanalization at all time points. Newly formed micro-thrombi were observed throughout the network, even after flow had been re-established. Vessels encountering impaired flow had an increased risk of developing a thrombus (reduced vs normal flow: RelativeRisk 2.4, p<0.0001; reversed vs normal flow: RelativeRisk 6.0, p<0.0001). Thrombosis risk in daughter vessels rose when a mother vessel contained a thrombus. Conclusions In conclusion, recanalization is insufficient to avert early and persistent vascular dysfunction in an MCA occlusion model. Our findings underscore the important role of pial artery impairment and underscore the need for complementary strategies to restore adequate blood flow and improve outcomes. Conflict of interest Moeed Khokhar: nothing to disclose