Current perspectives on the pathogenesis of cerebral atherosclerosis.

PURPOSE OF REVIEW: To summarize the current understanding of the pathogenesis of cerebral atherosclerosis to provide a basis for developing effective treatments and exploring future research directions for clinical application. RECENT FINDINGS: (1) Pathophysiological processes: Endothelial dysfunction and oxidative stress are crucial in the early stage of atherosclerotic plaque formation. Lipid accumulation, especially of low-density lipoprotein, promotes plaque growth and instability. Inflammatory responses exacerbate vascular damage, resulting in plaque rupture and thrombosis. (2) Genetic factors: Genetic studies have identified several loci associated with increased susceptibility to cerebral atherosclerosis, indicating potential therapeutic targets, including APOEε4, RNF213, NTNG1, and CYP2C19. (3) Daily diet also plays a role in the development of the disease. Healthy patterns (Mediterranean, DASH) with good nutrients and less bad fats/sodium can reduce cerebral atherosclerosis risk and improve cerebrovascular health. (1) This review presents recent progress in understanding the mechanisms of intracranial atherosclerosis, covering genetics, inflammation, comorbidities, diet, and exercise aspects. It reveals that managing blood pressure, lipids, glucose, and consistent moderate-intensity physical activity benefits vascular health. Controlling inflammation spread and maintaining cerebral vessel structure are linked to slowing the disease, suggesting therapeutic and genetic targets. (2) Nevertheless, there are gaps. Most mechanisms come from small-scale, single-center clinical studies, mainly focusing on extracranial atherosclerosis and plaque formation. Their reliability needs large-scale, multi-center validation. Besides, basic research is hampered by challenges of intracranial atherosclerosis animal models, like long duration, instability, and tissue-collecting difficulty. (3) Thus, large - scale clinical imaging can better describe intracranial atherosclerosis features. Also, specific animal models should be developed to offer more stable and reliable evidence and guidance for treating this disease.