Abstract: AIMS: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet preventive options remain limited. While resveratrol has demonstrated vascular protective effects in extracranial arteries, its role in preventing ICAS remains unclear. This study investigates whether resveratrol can attenuate the development of ICAS in a high-cholesterol rat model. METHODS: Adult male Sprague–Dawley rats were assigned to control or high-cholesterol diets, with or without resveratrol for up to 12 weeks. L-NAME was administered to high-cholesterol groups for the first 2 weeks to promote vascular injury. Blood lipids were measured at 3, 6, and 12 weeks. The middle cerebral artery (MCA) was assessed histologically for structural changes. Inflammatory and metabolic markers were analyzed by Western blot. RESULTS: The high-cholesterol diet induced significant increases in low-density lipoprotein, total cholesterol, and triglyceride levels, reduced high-density lipoprotein, and caused MCA narrowing and intimal thickening. These effects were markedly attenuated in resveratrol-treated rats. Resveratrol also reduced CD68 expression in the MCA, inhibited pro-inflammatory markers (monocyte chemoattractant protein-1, interferon-gamma, and vascular cell adhesion molecule-1), and upregulated protective pathways via SIRT1 and ABCA1 activation. CONCLUSIONS: Resveratrol prevents the onset of ICAS through anti-inflammatory and lipid-regulating mechanisms. Given the lack of effective therapies for ICAS and the widespread availability of resveratrol, these findings highlight its potential as a low-cost preventive strategy against stroke-related vascular pathology.
Shi et al. (Mon,) studied this question.