LEPTOMENINGEAL COLLATERALS DURING ISCHEMIC STROKE: A PRECLINICAL STUDY USING AWAKE FUNCTIONAL ULTRASOUND IMAGING TO CHARACTERIZE BLOOD FLOW PHENOMENA AND FUNCTIONAL RECOVERY

Stroke is the third leading cause of death worldwide. During ischemic stroke, occlusion causes cerebral blood flow (CBF) alteration, resulting in cell death and functional impairment. The leptomeningeal collaterals are vessels that connect vascular territories together, providing alternative blood pathways during occlusion. This collaterality varies greatly between patients and could be an important factor in the severity of stroke, but the specifics of their effects are unknown. Our aim is to characterize CBF and functional impact according to the degree of collaterality in the early and chronic phases of ischemic stroke.
This study includes two strains of mice, one rich and one poor in leptomeningeal collaterals. Stroke was performed with an awake thromboembolic model to overcome anesthetic bias. Treatment was rtPA (the only available drug in stroke today) or vehicle. Awake functional ultrasound imaging was performed to follow CBF and neurovascular phenomena in per-occlusion and chronically. This was added to the gold standard MRI at 24 hours.
Results show the expected drop in CBF, followed by inter-individual variability in perfusion profiles. Collateral-rich mice present gradual reperfusion and a good treatment response, with lesion size being significantly reduced compared to the other strain. At later time points, functional recovery was assessed by whisker stimulation and functional connectivity, showing functional recovery.
This is the first study to show these phenomena in awake condition, confirming the hypothesis that leptomeningeal collaterals allow better recovery and it improves our understanding of the vascular component of stroke.