Glymphatic pathway in sporadic cerebral small vessel diseases: From bench to bedside.

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.

Xu J ，Su Y ，Fu J ，Shen Y ，Dong Q ，Cheng X ... -  《-》

Pathogenesis of Cerebral Small Vessel Disease: Role of the Glymphatic System Dysfunction.

Lee DH ，Lee EC ，Park SW ，Lee JY ，Lee MR ，Oh JS ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Cerebral small vessel disease: neuroimaging markers and clinical implication.

Chen X ，Wang J ，Shan Y ，Cai W ，Liu S ，Hu M ，Liao S ，Huang X ，Zhang B ，Wang Y ，Lu Z ... -  《-》

Glymphatic clearance function in patients with cerebral small vessel disease.

Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to measure glymphatic function. We established modified index for diffusion tensor image analysis along the perivascular space (mALPS-index), which was calculated on diffusion tensor image (DTI), compared it with the classical detection of glymphatic clearance function calculated on Glymphatic MRI after intrathecal administration of gadolinium (study 1), and analyzed the relationship between CSVD imaging markers and mALPS-index in CSVD patients from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) (study 2). Among 39 patients included in study 1, mALPS-index were significantly related to glymphatic clearance function calculated on Glymphatic MRI ( r  = -0.772~-0.844, p < 0.001). A total of 330 CSVD patients were included in study 2. Severer periventricular and deep white matter hyperintensities (β = -0.332, p < 0.001; β = -0.293, p < 0.001), number of lacunas (β = -0.215, p < 0.001), number of microbleeds (β = -0.152, p = 0.005), and severer enlarged perivascular spaces in basal ganglia (β = -0.223, p < 0.001) were related to mALPS-index. Our results indicated that non-invasive mALPS-index might represent glymphatic clearance function, which could be applied in clinic in future. Glymphatic clearance function might play a role in the development of CSVD.

Zhang W ，Zhou Y ，Wang J ，Gong X ，Chen Z ，Zhang X ，Cai J ，Chen S ，Fang L ，Sun J ，Lou M ... -  《-》

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease.

Tian Y ，Zhao M ，Chen Y ，Yang M ，Wang Y ... -  《Biomolecules》