Abstract
Cerebral small vessels feed and protect the brain parenchyma thanks to the unique features of the blood–brain barrier. Cerebrovascular dysfunction is therefore seen as a detrimental factor for the initiation of several central nervous system (CNS) disorders, such as stroke, cerebral small vessel disease (cSVD), and Alzheimer’s disease. The main working hypothesis linking cerebrovascular dysfunction to brain disorders includes the contribution of neuroinflammation. While our knowledge on microglia cells – the brain-resident immune cells – has been increasing in the last decades, the specific populations of microglia and macrophages surrounding brain vessels, vessel-associated microglia (VAM), and perivascular macrophages (PVMs), respectively, have been overlooked. This review aims to summarize the knowledge gathered on VAM and PVMs, to discuss existing knowledge gaps of importance for later studies and to summarize evidences for their contribution to cerebrovascular dysfunction.
Highlights
A growing body of evidence supports the importance of our immune system in disease progression, making the research community more aware of the complexity of disease’s mechanisms but offering at the same time new diagnostic and therapeutic opportunities
The terms “perivascular microglia” and “perivascular macrophage,” given at several occasions, have not been always rightly used to describe immune cells associated with the cerebral vessels
The terms “vessel-associated microglia” (VAM) and “perivascular macrophages” (PVMs) will be first defined before summarizing the findings on VAM and PVMs associated with cerebrovascular diseases
Summary
A growing body of evidence supports the importance of our immune system in disease progression, making the research community more aware of the complexity of disease’s mechanisms but offering at the same time new diagnostic and therapeutic opportunities This holds true for cerebrovascular diseases such as cerebral small vessel disease (cSVD), the most prevalent cause of vascular cognitive impairment (Dichgans and Leys, 2017), in which the surroundings of brain small vessels are being scrutinized to decipher its exact pathophysiological mechanism. In this regard, perivascular immune cells have gained interest in the last three decades and both microglia and macrophages have been discussed in recent studies. Gene expression analyses and histological studies have reported cell-specific markers: TMEM119 (Transmembrane protein 119), P2RY12 (P2Y purinoceptor 12), SALL1 (Sallike protein 1), Siglec-H (Sialic acid-binding immunoglobulintype lectins), and Olfm (Olfactomedin 3) as microglia-specific markers, and CD163 and CD206 as CNS-macrophage-specific
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