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Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases, stroke, traumatic brain injury, and systemic diseases such as sepsis, viral and bacterial infections, and cancer. Compromised endothelial sealing leads to leaking blood vessels, followed by vasogenic edema. Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death. Brain microvascular endothelial cells, together with astrocytes, pericytes, microglia, and neurons form a selective barrier, the so-called blood-brain barrier, which regulates the movement of molecules inside and outside of the brain. Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood. Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years. One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3. In this review, we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.

Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss. In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients. Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use. Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier. Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.