Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Chinese Institute for Brain Research, Beijing 102206, China.
Biomolecules. 2022 May 25;12(6):748. doi: 10.3390/biom12060748.
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.
目前，全世界血管性认知障碍（vascular cognitive impairment，VCI）的发病率呈上升趋势，大多数研究表明，脑小血管病（cerebral small vessel disease，CSVD）是 VCI 的主要病因。有几个潜在的病理生理机制已被证明与 CSVD 过程有关，如血脑屏障损伤、小血管僵硬、静脉胶原化、脑血流减少、白质稀疏、慢性缺血、神经炎症、髓鞘损伤和随后的神经退行性变。然而，人们对这些机制的顺序和相对重要性的总体认识仍然有限。脑淋巴系统（glymphatic system，GS）和脑膜淋巴管（meningeal lymphatic vessels，mLVs）是中枢神经系统（central nervous system，CNS）中淋巴系统的类似物。因此，这些系统在调节脑脊液（cerebrospinal fluid，CSF）和细胞间液（interstitial fluid，ISF）转运、废物清除以及潜在的神经炎症方面发挥着关键作用。越来越多的证据表明，脑淋巴系统和脑膜淋巴管在 CSVD 的动物模型和 CSVD 患者中发挥着重要作用。鉴于 CSVD 的复杂性，了解 GS 和脑膜淋巴管转运与 CSVD 之间的潜在相互作用具有重要意义。在这里，我们提供了一个基于四大方面新进展的新框架，包括血管危险因素、潜在机制、临床亚型和认知，旨在解释脑淋巴系统和脑膜淋巴管如何促进 CSVD 的进展，并提出了一种全面的 CSVD 治疗策略的新见解。
