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Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial
Habibe Yılmaz1,2, Ulvi Bayraktutan1
1Academic Unit of Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham NG7 2UH, UK.
Insights
Cerebral small vessel disease (cSVD) is a common cause of stroke and dementia. This review examines if drugs for other neurovascular conditions can prevent cSVD by targeting neuroinflammation and oxidative stress.
Area of Science:
- Neuroscience
- Vascular Biology
- Pharmacology
Background:
- Cerebral small vessel disease (cSVD) is a primary cause of stroke and dementia.
- Key risk factors include aging, hypertension, hyperglycemia, and smoking, which induce oxidative stress and inflammation.
- cSVD manifests as white matter hyperintensities, microbleeds, and atrophy, with no current cure.
Purpose of the Study:
- To investigate if existing neurovascular drugs can prevent or delay cSVD progression.
- To explore the potential of these drugs in mitigating neuroinflammation and oxidative damage.
- To assess their efficacy in maintaining endothelial and blood-brain barrier integrity.
Main Methods:
- Systematic review of preclinical, translational, and clinical research.
- Analysis of drug classes including anti-anginals, ACE inhibitors, statins, lithium, PDE inhibitors, oral antihyperglycemics, and tetracyclines.
- Evaluation of drug mechanisms of action relevant to cSVD pathology.
Main Results:
- The review synthesizes evidence on how various drug classes impact pathways implicated in cSVD.
- Mechanisms explored include antioxidant, anti-inflammatory, and endothelial-protective effects.
- Preclinical and clinical data are critically assessed for potential therapeutic benefits in cSVD.
Conclusions:
- No definitive cure exists for cSVD, making prevention and delay crucial.
- Certain drug classes show promise in targeting cSVD mechanisms like neuroinflammation and oxidative stress.
- Further research is needed to establish the efficacy of these repurposed drugs for cSVD management.
Abstract:
Cerebral small vessel disease (cSVD) is a common cause of stroke and dementia. Ageing, hypertension, hyperglycaemia, and smoking make up the biggest risk factors for cSVD. They individually or collectively increase the levels of reactive oxygen species, pro-inflammatory cytokines and matrix metalloproteinases, decrease the bioavailability of nitric oxide, and, in the process, compromise the structural integrity and function of the vascular endothelium, blood-brain barrier, and brain parenchyma. These then appear as white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, and atrophy in cerebral imaging. As there is currently no curative therapy for cSVD, prevention or delay of cSVD remains of particular importance to preserve quality of life for as long as possible. Bearing that in mind, this review explores whether drugs used for other neurovascular conditions may prevent neuroinflammation and oxidative damage and effectively maintain endothelial function and blood-brain barrier integrity. It also examines whether potential benefits may be extended to cSVD. The list of drugs includes anti-anginal drugs, acetylcholine esterase inhibitors, β-hydroxy β-methylglutaryl-CoA reductase inhibitors, lithium drugs, phosphodiesterase inhibitors, oral antihyperglycaemic drugs, and tetracycline antibiotics. This review discusses the mechanisms of action of these agents and critically evaluates preclinical, translational, and clinical research pertaining to cSVD.
