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

Abstract

There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main contributor to VCI. Several potential physiopathologic mechanisms have been proven to be involved in the process of CSVD, such as blood-brain barrier damage, small vessels stiffening, venous collagenosis, cerebral blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin damage, and subsequent neurodegeneration. However, there still is a limited overall understanding of the sequence and the relative importance of these mechanisms. The glymphatic system (GS) and meningeal lymphatic vessels (mLVs) are the analogs of the lymphatic system in the central nervous system (CNS). As such, these systems play critical roles in regulating cerebrospinal fluid (CSF) and interstitial fluid (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence has suggested that the glymphatic and meningeal lymphatic vessels played vital roles in animal models of CSVD and patients with CSVD. Given the complexity of CSVD, it was significant to understand the underlying interaction between glymphatic and meningeal lymphatic transport with CSVD. Here, we provide a novel framework based on new advances in main four aspects, including vascular risk factors, potential mechanisms, clinical subtypes, and cognition, which aims to explain how the glymphatic system and meningeal lymphatic vessels contribute to the progression of CSVD and proposes a comprehensive insight into the novel therapeutic strategy of CSVD.

Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study

“…42 Third, many pathogenic mechanisms of CSVD, including neurovascular unit dysfunction, blood-brain barrier (BBB) damage and haemodynamic dysfunction, resulted in interstitial solute deposition in the brain parenchyma and impaired glymphatic system. 43 The excessive perivascular accumulation of cell debris and metabolic wastes due to impaired glymphatic clearance in turn aggravated decreased cerebrovascular reactivity, BBB disruption and enhanced perivascular inflammation. Ultimately, a vicious circle was produced between glymphatic dysfunction and aforementioned mechanisms that may exacerbate the CSVD pathology.…”

Idiopathic intracranial hypertension in patients with cerebral small vessel disease: A case report

“…[ 14 ] Our understanding of the potential physiopathological mechanisms of CSVD is still limited; recent studies have shed light on the role of the glymphatic and meningeal lymphatic systems in CSVD. [ 36 ] Impairment of the glymphatic system and lymphatic CSF drainage has been proven to be associated with cerebrovascular risk factors strongly linked to CSVD, including aging, hypertension, diabetes, and lipid metabolism. This condition supports the potential role of glymphatic and lymphatic system dysfunction in CSVD.…”

“…This condition supports the potential role of glymphatic and lymphatic system dysfunction in CSVD. [ 36 ] In addition, hypertension, a significant risk factor for CSVD, can cause decreased glymphatic function.…”

Correction: Tian et al. The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease. Biomolecules 2022, 12, 748

“…In the published publication [ 1 ], there was a mistake in the legend for Figure 2. The legend of Figure 2 was wrongly consistent with that of Figure 1.…”