Epigenetics in blood-brain barrier disruption

Abstract

The vessels of the central nervous system (CNS) have unique barrier properties. The endothelial cells (ECs) which comprise the CNS vessels contribute to the barrier via strong tight junctions, specific transporters, and limited endocytosis which combine to protect the brain from toxins and maintains brain homeostasis. Blood-brain barrier (BBB) leakage is a serious secondary injury in various CNS disorders like stroke, brain tumors, and neurodegenerative disorders. Currently, there are no drugs or therapeutics available to treat specifically BBB damage after a brain injury. Growing knowledge in the field of epigenetics can enhance the understanding of gene level of the BBB and has great potential for the development of novel therapeutic strategies or targets to repair a disrupted BBB. In this brief review, we summarize the epigenetic mechanisms or regulators that have a protective or disruptive role for components of BBB, along with the promising approaches to regain the integrity of BBB.

Keywords: Blood–brain barrier; DNA methylation; Endothelial cells; Epigenetics; Histone modifications.

Fig. 1

Diagrammatic representation of a neurovascular unit (NVU). NVU consisting of vascular cells, glial cells and neurons are shown in a, and the enlarged view of the inset is given in b. Endothelial cells (red), pericytes (blue), and smooth muscle cells (pale green) represent the vascular cells. The glia cells are given in dark green (astrocytes), and blue (oligodendrocytes), yellow (microglia) and the neurons in pink color. Tight junctions connecting the endothelial cells are also shown in b