Cerebral Vascular Diameter and Flow Irregularities Due to Ischemic Stroke After Middle Cerebral Artery Occlusion

Acute ischemic stroke is a major cause of death and disability. Although reperfusion therapies are effective, early and lasting alterations in the microvasculature can limit recovery. Research has largely focused on microvascular impairment, while the pial arterial network remains relatively underexplored. Using the middle cerebral artery occlusion model and in vivo microscopy in mice, we assessed pial vessel dynamics during occlusion, recanalization, and the first 24 hours of reperfusion. We analysed vessel diameter, irregularity, resistance, blood flow, and micro-thrombus formation. Results revealed marked vasoconstriction throughout the pial network during occlusion, which persisted after recanalization, with vessel diameters reduced to 72% ±27% (SD) of baseline at 24 hours. Smaller pial vessels (<30µm) reacted differently over time compared to larger vessels. Vessel irregularity and resistance increased and peaked at 24 hours. A considerable proportion of vessels had impaired flow and micro-thrombi at all timepoints. Thrombosis risk in daughter vessels rose when a mother vessel contained a thrombus. In conclusion, recanalization is insufficient to avert early and persistent vascular dysfunction in this model. Our findings underscore the role of pial artery impairment in disturbed reperfusion and point to the need for complementary strategies to restore adequate blood flow and improve outcomes.