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Published on: July 29, 2019
Glymphatic pathway in sporadic cerebral small vessel diseases: From bench to bedside
1Department of Neurology, National Center for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Insights
Cerebral small vessel diseases (CSVD) may stem from impaired glymphatic pathway clearance. This review explores glymphatic failure in CSVD pathogenesis and potential therapeutic targets.
Area of Science:
- Neurology
- Neuroscience
- Vascular Biology
Background:
- Cerebral small vessel diseases (CSVD) are heterogeneous, involving intracranial small blood vessels.
- Traditional pathogenesis theories (endothelial dysfunction, blood-brain barrier leakage, inflammation) incompletely explain CSVD.
- The glymphatic pathway's role in clearing brain waste is a recent discovery offering new insights.
Purpose of the Study:
- To review cerebral small vessel diseases (CSVD) and the glymphatic pathway.
- To elucidate CSVD pathogenesis through the lens of glymphatic pathway dysfunction.
- To explore potential clinical applications targeting the glymphatic pathway for CSVD therapies.
Main Methods:
- Review of existing literature on CSVD and glymphatic pathway function.
- Analysis of basic animal models investigating glymphatic failure in CSVD.
- Examination of clinical neuroimaging markers associated with glymphatic dysfunction in CSVD.
Main Results:
- Glymphatic pathway dysfunction is proposed as a key factor in CSVD pathogenesis.
- Animal models and neuroimaging data support the link between glymphatic failure and CSVD.
- Dysfunction in perivascular clearance may underlie the complex features of CSVD.
Conclusions:
- Glymphatic failure offers a novel perspective on the pathogenesis of cerebral small vessel diseases.
- Targeting the glymphatic pathway presents promising avenues for future CSVD therapies and prevention strategies.
- Further research into glymphatic function could revolutionize the management of CSVD.
Abstract:
Cerebral small vessel diseases (CSVD) consist of a group of diseases with high heterogeneity induced by pathologies of intracranial small blood vessels. Endothelium dysfunction, bloodbrain barrier leakage and the inflammatory response are traditionally considered to participate in the pathogenesis of CSVD. However, these features cannot fully explain the complex syndrome and related neuroimaging characteristics. In recent years, the glymphatic pathway has been discovered to play a pivotal role in clearing perivascular fluid and metabolic solutes, which has provided novel insights into neurological disorders. Researchers have also explored the potential role of perivascular clearance dysfunction in CSVD. In this review, we presented a brief overview of CSVD and the glymphatic pathway. In addition, we elucidated CSVD pathogenesis from the perspective of glymphatic failure, including basic animal models and clinical neuroimaging markers. Finally, we proposed forthcoming clinical applications targeting the glymphatic pathway, hoping to provide novel ideas on promising therapies and preventions of CSVD.
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