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Abstract
Neurons are extremely vulnerable cells that tightly rely on the brain’s highly dynamic and complex vascular network that assures an accurate and adequate distribution of nutrients and oxygen. The neurovascular unit (NVU) couples neuronal activity to vascular function, controls brain homeostasis, and maintains an optimal brain microenvironment adequate for neuronal survival by adjusting blood-brain barrier (BBB) parameters based on brain needs. The NVU is a heterogeneous structure constituted by different cell types that includes pericytes. Pericytes are localized at the abluminal side of brain microvessels and contribute to NVU function. Pericytes play essential roles in the development and maturation of the neurovascular system during embryogenesis and stability during adulthood. Initially, pericytes were described as contractile cells involved in controlling neurovascular tone. However, recent reports have shown that pericytes dynamically respond to stress induced by injury upon brain diseases, by chemically and physically communicating with neighboring cells, by their immune properties and by their potential pluripotent nature within the neurovascular niche. As such, in this paper, we would like to review the role of pericytes in NVU remodeling, and their potential as targets for NVU repair strategies and consequently neuroprotection in two pathophysiologically distinct brain disorders: ischemic stroke and Alzheimer’s disease (AD).
Highlights
The brain consumes up to 20% of nutrients—mainly glucose—and oxygen present in the blood [1].neurons totally rely on the brain’s highly dynamic and complex vascular network that assures an accurate and adequate distribution of oxygen and glucose [2]
The blood-brain barrier (BBB) is formed by tightly sealed endothelial cells, constituting a non permissive physical barrier that separates the blood from the brain
neurovascular unit (NVU) is constituted by specialized endothelial cells, which form the blood-brain barrier (BBB), that actively interact with the basal lamina, pericytes, astrocyte-endfeet, microglia and neurons
Summary
The brain consumes up to 20% of nutrients—mainly glucose—and oxygen present in the blood [1]. The BBB is formed by tightly sealed endothelial cells, constituting a non permissive physical barrier that separates the blood from the brain. Brain endothelial cells actively interact with extracellular matrix proteins forming the basal lamina, pericytes, astrocytes, microglia and neurons, forming all together the neurovascular unit (NVU) that couples neuronal activity to vascular function by controlling regional. Pericytes are required for a proper brain vascularization during the embryonic stage, mainly by stabilizing the newly formed vessels [8] and by inducing BBB functional properties during the early postnatal stage [9]. We will briefly review the role of pericytes in brain vascular network formation, and will describe the response of pericytes to NVU injury in two brain disorders that are pathophysiologically different, which are ischemic stroke and Alzheimer’s disease (AD). We will outline the potential of pericytes as targets for innovative therapeutic approaches that aim to restore NVU function, and rescue neuronal function in these two brain disorders
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