Cerebral small vessel disease: targeting oxidative stress as a novel therapeutic strategy?

De Silva, T. M. and Miller, A. A. (2016) Cerebral small vessel disease: targeting oxidative stress as a novel therapeutic strategy? Frontiers in Pharmacology, 7, 61. (doi: 10.3389/fphar.2016.00061) (PMID:27014073) (PMCID:PMC4794483)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Dr Alyson
• Authors: De Silva, T. M., and Miller, A. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Frontiers in Pharmacology
• Publisher: Frontiers Media
• ISSN: 1663-9812
• ISSN (Online): 1663-9812
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Frontiers in Pharmacology 7:61
• Publisher Policy: Reproduced under a Creative Commons License