Vascular dementia (VaD) is the leading cause of cognitive decline resulting from vascular lesions. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. The aim of the present study was to evaluate the beneficial effects of resveratrol-loaded solid lipid nanoparticles (R-SLNs) in permanent bilateral common carotid artery occlusion (BCCAO) induced model of VaD. R-SLNs prepared had average size of 286 nm and 91.25% drug encapsulation efficiency with sustained release. Moreover, R-SLNs had 4.5 times higher levels of resveratrol (RSV) in brain compared to when administered as free RSV. Neurobehavioral analyses revealed that R-SLNs administration successfully ameliorated cognitive decline observed in BCCAO rats. Administration of R-SLNs to BCCAO animals showed significant reduction in mitochondrial reactive oxygen species (ROS) generation, lipid peroxidation, and protein carbonyls. In addition, R-SLNs significantly improved redox ratio and Mn-superoxide dismutase (Mn-SOD) activity. R-SLNs administration resulted in significant reduction in hypoxia-inducible factor 1α (HIF-1α) levels, whereas, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were increased after R-SLNs treatment. Taken together, the results demonstrate that R-SLNs could be a novel and promising therapeutic strategy in VaD as well in other age-related neurodegenerative disorders.

血管性痴呆（VaD）是由血管病变引起的认知能力下降的主要原因。最近的研究表明，线粒体功能障碍和氧化应激与认知能力下降有关。本研究的目的是评估白藜芦醇负载的固体脂质纳米颗粒（R-SLNs）在永久性双侧颈总动脉闭塞（BCCAO）诱导的VaD模型中的有益作用。制备的R-SLN的平均大小为286 nm，药物包封效率为91.25％，且具有持续释放。此外，R-SLNs在大脑中的白藜芦醇（RSV）含量比以游离RSV给药时高4.5倍。神经行为分析表明，R-SLNs的给药成功改善了BCCAO大鼠的认知能力下降。向BCCAO动物施用R-SLNs显示线粒体活性氧（ROS）生成，脂质过氧化和蛋白质羰基的显着减少。此外，R-SLNs显着提高了氧化还原比和Mn-超氧化物歧化酶（Mn-SOD）活性。R-SLNs给药导致缺氧诱导因子1α（HIF-1α）水平显着降低，而核因子（类胡萝卜素衍生的2）样2（Nrf2）和血红素加氧酶1（HO-1）的水平升高。 R-SLNs处理。两者合计，结果表明R-SLNs可能是VaD以及其他与年龄相关的神经退行性疾病的一种新颖且有希望的治疗策略。R-SLNs显着提高了氧化还原比和Mn-超氧化物歧化酶（Mn-SOD）活性。R-SLNs给药导致缺氧诱导因子1α（HIF-1α）水平显着降低，而核因子（类胡萝卜素衍生的2）样2（Nrf2）和血红素加氧酶1（HO-1）的水平升高。 R-SLNs处理。两者合计，结果表明R-SLNs可能是VaD以及其他与年龄相关的神经退行性疾病的一种新颖且有希望的治疗策略。R-SLNs显着提高了氧化还原比和Mn-超氧化物歧化酶（Mn-SOD）活性。R-SLNs给药导致缺氧诱导因子1α（HIF-1α）水平显着降低，而核因子（类胡萝卜素衍生的2）样2（Nrf2）和血红素加氧酶1（HO-1）的水平升高。 R-SLNs处理。两者合计，结果表明R-SLNs可能是VaD以及其他与年龄相关的神经退行性疾病的一种新颖且有希望的治疗策略。