Abstract

Brain endothelial cells constitute the major cellular element of the highly specialized blood-brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammation.-Lopez-Ramirez, M. A., Reijerkerk, A., de Vries, H. E., Romero, I. A. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation.

Highlights

  • Brain endothelial cells (BECs) constitute the major cellular element of the highly specialized blood–brain barrier (BBB) that is essential for CNS homeostasis

  • Our study further suggests that increased levels of brain endothelial microRNA-155 contribute to early BBB impartment observed during neuroinflammation

  • Cytokines regulate the expression of brain endothelial microRNAs that either promote or inhibit inflammatory pathways to orchestrate neuroinflammation at the cerebrovascular bed

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Summary

INTRODUCTION

Brain endothelial cells (BECs) constitute the major cellular element of the highly specialized blood–brain barrier (BBB) that is essential for CNS homeostasis. The cerebral microvasculature formed by BECs constitutes an elaborate network of vessels that is composed of arterioles (10–100 mm in diameter), capillaries (4–10 mm in diameter), and venules (10–100 mm in diameter), which allows transport of nutrients and gases and removal of waste products throughout the brain and spinal cord [1]. BECs play an important role in maintaining blood flow and limiting entry of circulating leukocytes and blood-borne molecules into the CNS. ABBREVIATIONS: BBB, blood–brain barrier; BEC, brain endothelial cell; CCL2, chemokine ligand 2; EAE, experimental autoimmune encephalomyelitis; Egfl, epidermal growth factor–like-7; ICAM-1, intracellular cell adhesion molecule 1; MS, multiple sclerosis; TJ, tight junction

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