Hypoxia‐induced blood‐brain barrier dysfunction is prevented by pericyte‐conditioned media via attenuated actomyosin contractility and claudin‐5 stabilization

Abstract

The blood‐brain barrier (BBB) regulates molecular and cellular entry from the cerebrovasculature into the surrounding brain parenchyma. Many diseases of the brain are associated with dysfunction of the BBB, where hypoxia is a common stressor. However, the contribution of hypoxia to BBB dysfunction is challenging to study due to the complexity of the brain microenvironment. In this study, we used a BBB model with brain microvascular endothelial cells and pericytes differentiated from iPSCs to investigate the effect of hypoxia on barrier function. We found that hypoxia‐induced barrier dysfunction is dependent upon increased actomyosin contractility and is associated with increased fibronectin fibrillogenesis. We propose a role for actomyosin contractility in mediating hypoxia‐induced barrier dysfunction through modulation of junctional claudin‐5. Our findings suggest pericytes may protect brain microvascular endothelial cells from hypoxic stresses and that pericyte‐derived factors could be candidates for treatment of pathological barrier‐forming tissues.

Exosomes are involved in iron transport from human blood–brain barrier endothelial cells and are modified by endothelial cell iron status

“…Thus, the impact of iron chelation on exosomal membrane proteins may be both indirect as well as direct. It should be noted, however, that hypoxia reportedly reduces the TEER values in the BBB model ( 52 ). In our study, we did not see any effect of DFO treatment on TEER values compared to the control or FAC treatments, suggesting hypoxia is an unlikely explanation for the effect on the exosome release.…”

A year in review: brain barriers and brain fluids research in 2022

“…The interaction suppressed endothelial transcytosis. Pericytes can produce factors that protect the BBB from hypoxia [ 17 ]. Sancho et al [ 18 ] have recently provided evidence that K ATP channels are important regulators of pericyte and brain endothelial cell membrane potentials and that adenosine activates those channels via A 2A receptors with important implications for brain blood flow regulation.…”

Aging Increases Hypoxia-Induced Endothelial Permeability and Blood-Brain Barrier Dysfunction by Upregulating Arginase-II

“…All of these situations are highly associated with aging [4]. Hypoxia is known to induce BBB breakdown, leading to neurological disorders [5,6]. Among the endothelial cell-cell junctional proteins, the TJ protein Zonula occludens-1 cadherin are arguable of dominant importance [7].…”