Pericytes and Neurovascular Function in the Healthy and Diseased Brain

Abstract

Pericytes are multi-functional cells embedded within the walls of capillaries throughout the body, including the brain. Pericytes were first identified in the 1870s, but little attention was paid to them during the following century. More recently, numerous vascular functions of pericytes have been identified including regulation of cerebral blood flow, maintenance of the blood-brain barrier (BBB), and control of vascular development and angiogenesis. Pericytes can also facilitate neuroinflammatory processes and possess stem cell-like properties. Pericytes form part of the neurovascular unit (NVU), a collection of cells that control interactions between neurons and the cerebral vasculature to meet the energy demands of the brain. Pericyte structure, expression profile, and function in the brain differ depending on their location along the vascular bed. Until recently, it has been difficult to accurately define the sub-types of pericytes, or to specifically target pericytes with pharmaceutical agents, but emerging techniques both in vitro and in vivo will improve investigation of pericytes and allow for the identification of their possible roles in diseases. Pericyte dysfunction is increasingly recognized as a contributor to the progression of vascular diseases such as stroke and neurodegenerative diseases such as Alzheimer’s disease. The therapeutic potential of pericytes to repair cerebral blood vessels and promote angiogenesis due to their ability to behave like stem cells has recently been brought to light. Here, we review the history of pericyte research, the present techniques used to study pericytes in the brain, and current research advancements to characterize and therapeutically target pericytes in the future.

The Amyloid-Tau-Neuroinflammation Axis in the Context of Cerebral Amyloid Angiopathy

“…The neurovascular unit (NVU) is a complex structure organized by endothelial cells, intimately associated with pericytes and astrocytic endfeet to form the BBB. Parenchymal cells including excitatory neurons, regulatory interneurons and microglia actively interact with the NVU [121]. As central components of the NVU, pericytes represent the first line of immunological defense as antigen-presenting cells, playing a pivotal role in the maintenance of the BBB and microvascular stability.…”

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

“…These cells were originally described in late 19th century (Eberth, 1871;Rouget, 1873) and initially named "pericytes" in 1923 by Zimmermann (Zimmermann, 1923) in accordance with their location enveloping the endothelium, and their being embedded in the basement membrane outside the microvessels (Zimmermann, 1923;Armulik et al, 2011;Geranmayeh et al, 2019). Although pericytes were considered to contribute to architectural maintenance and contraction of capillaries (Sandison, 1931;Zweifach, 1934;Clark and Clart, 1940), little had been known about their multifunctional characteristics and roles in neurological disorders until late 20th century (Brown et al, 2019). In the last 20 years, however, using a combination of markers and advancing technologies, a variety of functions of pericytes in health and disease have been revealed.…”

This was the year that was: brain barriers and brain fluid research in 2019

“…The importance of the pericyte at the NVU has become evident in recent years [32]. For example, Nikolakopoulou et al [33] have now shown that pericyte ablation results in vascular dysfunction, including BBB breakdown and reduced blood flow, and neuronal loss.…”