A piece of evidence for pathogenesis of cerebral small vessel disease caused by blood-brain barrier dysfunction

Abstract

BackgroundBlood-brain barrier (BBB) dysfunction caused by endothelial cell injury is one of the widely accepted pathogenesis of small cerebral vessel disease (CSVD). However, the early microcirculation studies were notably deficient in providing compelling imaging evidence, which has hampered a comprehensive understanding of the pathophysiological processes underlying BBB dysfunction in CSVD. The onset of CSVD is insidious and the clinical manifestations are diverse, diagnosis of CSVD relies primarily on neuroimaging information currently. These MRI imaging features mainly represent the end-stage brain parenchyma injury, rather than the vascular lesion itself. Therefore, clarifying the pathophysiological processes related to cerebral microcirculation in CSVD is of great significance for early treatment intervention of CSVD. MethodsTwenty rats were used to prepare CSVD animal model by ultrasound combined with ultrasonic microbubble contrast agent. MRI, functional ultrasound (fUS) imaging and ultrasound localization microscopy (ULM) were used to evaluate microcirculation changes in acute and chronic models. ResultsCurrently, our research has successfully validated that the imaging characteristics of this model align with the four established criteria outlined in the STRIVE-2 classification. FUS shows increased microflow velocity in the molding area, which can be used for initial evaluation of CSVD models in the acute phase. ULM has revealed a progressive reduction in the density of both the short cortical arteries and the long medullary arteries, along with their respective branches, over time. Concurrently, there has been a noted deviation in blood flow velocity. ConclusionThis model offers compelling evidence at the microvascular level, suggesting that blood-brain barrier (BBB) dysfunction is a central pathophysiological mechanism in the etiology of CSVD. Then it provides a straightforward, efficient, and widely applicable tool and continuous monitoring method for the further investigation of CSVD from the macroscopic to the microscopic circulation level, with significant long-term implications for CSVD diagnosis and treatment.