Seeing the Small to Prevent the Big: The Role of Cerebral Microvessels in Ischemic Stroke Etiology and Prevention

Abstract

Despite decades of progress in its management, ischemic stroke remains a leading cause of death and disability worldwide, with incidence rising in younger populations. Although traditional stroke risk assessment focuses on macrovascular pathology, the cerebral microcirculation plays an important but less‐recognized role. This review synthesizes evidence on microvascular involvement in the pathogenesis of ischemic stroke and evaluates existing and emerging methods for microvascular assessment of ischemic stroke risk (MvASR). Epidemiological studies show that cerebral small vessel disease as measured by MRI biomarkers significantly increase stroke risk, with risk rising alongside lesion progression. Microemboli animal models reveal that even asymptomatic microemboli can disrupt the blood‐brain barrier and trigger inflammatory changes that may predispose to stroke. Postischemia models demonstrate that no‐reflow and prolonged microvascular inflammation compromise patency, potentially increasing recurrent stroke risk. Current MvASR modalities can be classified into direct imaging (cerebral angiography, retinal photography), indirect imaging (MRI, transcranial Doppler), and nonimaging approaches (e.g., genetic testing for CADASIL). Although more studies demonstrating clinical utility are needed, the accumulating pathophysiological and epidemiological evidence suggests that MvASR will become increasingly relevant to stroke prediction and prevention.