Neuroinflammation and blood–brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications

Cerebral small vessel disease (CSVD) is a chronic, progressive cerebrovascular disorder affecting small arteries, arterioles, venules, and capillaries, and is a leading contributor to stroke, vascular dementia, and cognitive impairment. Accumulating evidence has revealed that the pathogenesis of CSVD is multifactorial, with neuroinflammation and blood-brain barrier (BBB) dysfunction emerging as central pathological processes. Notably, a bidirectional feedback loop between neuroinflammation and BBB breakdown has been identified. Endothelial cells, microglia, oligodendrocytes, as main cell components in maintaining the physiological functions of BBB performed significant roles. Imaging modalities have improved detection of BBB permeability changes and CSVD progression. Recent translational research has identified potential biomarkers for early diagnosis. Therefore, some new therapeutic approaches targeting the neuroinflammation-BBB axis can provide better early intervention for CSVD and have superior therapeutic effects. In our review, we first elaborated on the pathological role of CSVD, particularly emphasizing the importance of the integrity of the BBB. Then, we highlighted the clinical characteristics and translational research evidence of CSVD, including novel imaging and biochemical biomarkers, potential therapeutic approaches, and the progress of preclinical models, thereby revealing the research progress of CSVD.