Agrin, Aquaporin-4, and Astrocyte Polarity as an Important Feature of the Blood-Brain Barrier

Abstract

The blood-brain barrier (BBB) does not exclusively refer to brain endothelial cells, which are the site of the barrier proper. In the past few years, it has become increasingly clear that BBB endothelial cells depend considerably on the brain microenvironment to a degree exceeding the environmental influence in other organs. The concept of the BBB has been continuously developed over the decades, culminating now in the recognition that endothelial cell function in the brain is not limited to simply mediating energy and oxygen transfer between blood and neural tissue. Endothelial cells are rather "Janus-headed beings" that are active partners of both luminal molecules and cells, as well as subendothelial cells such as pericytes, astrocytes, and neurons. In this overview, the authors present and discuss both the role of astroglial cells in managing the BBB and aspects of pathological alterations in the brain as far as the BBB is involved. After a brief introduction of the BBB that describes the structure and function of the brain capillary endothelial cells, the authors report on both the water channel protein aquaporin-4 (AQP4) in astrocytes and the extracellular matrix between astrocytes/pericytes and endothelial cells. The AQP4 has an important impact on the homeostasis in the brain parenchyma; however, the mechanistic cascade from the composition of the astrocyte membrane to the maintenance of BBB properties in the endothelial cells, including their tight junction formation, is still completely unknown.

Extracellular matrix and matrix receptors in blood–brain barrier formation and stroke

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Disruption of blood-brain barrier in amyotrophic lateral sclerosis: an update

“…Part of the astrocytic membrane that adjoins the basal membrane and endothelium has a large number of proteins (aquaporin 4) that form water channels. Dysfunction of these proteins or dis ruption of the pattern of their location in astrocytic membrane may result in the formation or enhance ment of edema [36,37].…”

Yixinshu ameliorates hippocampus abnormality induced by heart failureviathe PPARγ signaling pathway

“…Aquaporin-4 (AQP4) is a water channel protein that can reconcile the homeostasis of water in the BBB. 16,17 Neuro-inammation is a hallmark that induces alterations in brain structure and function in major depressive disorders.…”