De Silva T Michael, Miller Alyson A
Department of Pharmacology, Biomedicine Discovery Institute, Monash University Melbourne, VIC, Australia.
Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University Melbourne, VIC, Australia.
Front Pharmacol. 2016 Mar 17;7:61. doi: 10.3389/fphar.2016.00061. eCollection 2016.
Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors.
脑小血管病（SVD）是中风的主要成因，也是认知障碍和痴呆的主要原因。尽管脑SVD具有破坏性影响，但其发病机制仍未完全明确。此外，尚无针对其预防或治疗的特异性药理学策略。脑SVD的特征是脑微循环存在明显的功能和结构异常。这些病理变化的临床表现包括腔隙性梗死、白质高信号和脑微出血。本综述的主要目的是讨论氧化应激与非淀粉样和淀粉样（脑淀粉样血管病）形式的脑SVD的动脉病变及其最重要的危险因素（高血压和衰老）之间的关联证据，以及氧化应激对脑SVD相关脑损伤和认知障碍的影响。我们还强调了目前关于NADPH氧化酶参与氧化应激发展的证据，这些酶是脑血管中活性氧的主要来源。最后，我们讨论了针对脑SVD氧化应激的潜在药理学策略，包括一些历史上和新兴的NADPH氧化酶抑制剂。
