Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation.
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.
Department of Medicine, University of California, San Diego, La Jolla, California, USA;
Miguel Alejandro
MA
Lopez-Ramirez
Pluriomics B.V., Leiden, The Netherlands;
Arie
A
Reijerkerk
Blood-Brain Barrier Research Group, Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands;
Helga E
HE
de Vries
Department of Life, Health, and Chemical Sciences, Biomedical Research Network, The Open University, Milton Keynes, United Kingdom i.romero@open.ac.uk.
Ignacio Andres
IA
Romero
D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs
inflammation; multiple sclerosis; neurovascular unit; regulatory mechanisms; stroke