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Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?
T Michael De Silva1, Alyson A Miller2
1Department of Pharmacology, Biomedicine Discovery Institute, Monash University Melbourne, VIC, Australia.
Insights
Oxidative stress contributes to cerebral small vessel disease (SVD), a cause of stroke and cognitive decline. Targeting NADPH oxidases may offer new treatments for SVD and related brain injuries.
Area of Science:
- Neurology
- Vascular Biology
- Oxidative Stress Research
Background:
- Cerebral small vessel disease (SVD) significantly contributes to stroke, cognitive impairment, and dementia.
- Pathogenesis of SVD remains incompletely understood, with no specific treatments available.
- SVD involves microcirculation abnormalities, leading to lacunar infarcts, white matter hyperintensities, and microbleeds.
Purpose of the Study:
- To review evidence linking oxidative stress to cerebral SVD, including its risk factors and contribution to brain injury.
- To discuss the role of NADPH oxidases as a key source of reactive oxygen species in cerebral vasculature.
- To explore potential pharmacological strategies targeting oxidative stress in SVD.
Main Methods:
- Literature review of studies on cerebral SVD, oxidative stress, and NADPH oxidases.
- Analysis of evidence implicating oxidative stress in SVD arteriopathy and risk factors (hypertension, aging).
- Examination of research on NADPH oxidase involvement in SVD pathogenesis and potential therapeutic interventions.
Main Results:
- Oxidative stress is implicated in both amyloid and non-amyloid forms of cerebral SVD.
- Hypertension and aging are significant risk factors associated with increased oxidative stress in SVD.
- NADPH oxidases are identified as major contributors to oxidative stress in the cerebral vasculature.
Conclusions:
- Oxidative stress plays a crucial role in the development and progression of cerebral SVD.
- NADPH oxidase inhibitors represent a promising therapeutic avenue for managing SVD and its neurological consequences.
- Further research into targeting oxidative stress pathways is essential for effective SVD prevention and treatment.
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.
