Pathophysiological Mechanisms and Therapeutic Targets in Cerebral Small Vessel Disease: A Comprehensive Review

Abstract:

Cerebral Small Vessel Disease (CSVD) is a dynamic whole-brain disease, characterized by pathological cascades that affect the brain's venules, capillaries, small arteries, and arterioles. Neuroimaging features of CSVD typically comprise Recent Small Subcortical Infarcts (RSSI), lacunes of presumed vascular origin, White Matter Hyperintensities (WMH) of presumed vascular origin, enlarged Perivascular Spaces (PVS), Cerebral Microbleeds (CMB), and Brain Atrophy (BA). The main clinical features of CSVD often include stroke, abnormal gait, psychiatric disorders, cognitive decline, and urinary incontinence, imposing a heavy burden on individuals and society. Despite its impact, the pathogenesis of CSVD remains unclear, and current clinical diagnosis relies primarily on neuroimaging, presenting considerable challenges for effective treatment. In recent years, most studies have addressed the pathophysiological and molecular mechanisms of CSVD, including chronic cerebral hypoperfusion, inflammatory cascades, oxidative stress, endothelial dysfunction, and Blood-Brain Barrier (BBB) leakage. In addition, genetic factors have been strongly associated with CSVD, though genetic heterogeneity and the complexity of internal environment homeostasis contribute to the persistent uncertainty surrounding its exact mechanisms. A comprehensive overview of these individual mechanisms is crucial for a holistic understanding of the pathogenesis of CSVD. Currently, there is a relative lack of therapeutic drugs and interventions for the complex pathogenesis of CSVD. The existing treatments, such as antihypertensives, antiplatelet agents, lipid-lowering drugs, and hypoglycemic agents, along with traditional alternative therapies like Chinese herbal medicine and acupuncture, have demonstrated efficacy in modulating the occurrence and progression of CSVD. These therapies provide a new perspective for developing more rational CSVD prevention strategies and treatment plans. This review systematically summarizes the cutting-edge research achievements in the field of pathological and physiological mechanisms of CSVD over the past few years, as well as potential treatment pathways and limitations, to provide a theoretical basis and intervention directions for the diagnosis and treatment of this patient population.