JCI table of contents: Dec. 20, 2007

Hypertensive encephalopathy is an often-fatal disease of the brain that results from extremely high blood pressure. This disorder can lead to a breakdown of the blood-brain barrier (BBB), resulting in fluid accumulation in the brain, a condition known as cerebral edema. The mechanisms underlying the breakdown of the BBB were previously unknown. However, a new study by Daria Mochly-Rosen and colleagues from Stanford University School of Medicine has revealed a role for activation of the protein PKC in dysregulation of the integrity of the BBB leading to hypertensive encephalopathy. Furthermore, their studies suggest that delta-PKC may be a useful therapeutic target in patients at risk for developing hypertensive encephalopathy.

Dahl salt-sensitive (DS) rats, when fed a high-salt diet from a young age, often develop severely high blood pressure, encephalopathy, and cerebral edema. The authors found that encephalopathy, BBB disruption, and mortality rates all decreased when PKC was inhibited in hypertensive DS rats. These effects seemed to be due to decreased disruption of the small blood vessels located in the brain. In an accompanying commentary, Robert Messing and Wen-Hai Chou from the University of California at San Francisco, Emeryville, suggest that these results provide incentive to investigate whether PKC signaling pathways mediate BBB dysfunction in other disease states.

TITLE: Sustained pharmacological inhibition of delta-PKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats

AUTHOR CONTACT:
Daria Mochly-Rosen
Stanford University School of Medicine, Stanford, California, USA.
Phone: (650) 725-7720; Fax: (650) 723-4686; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32636

ACCOMPANYING COMMENTARY TITLE: Hypertensive encephalopathy and the blood-brain barrier: is delta-PKC a gatekeeper?

AUTHOR CONTACT:
Robert O. Messing
University of California at San Francisco, Emeryville, California, USA.
Phone: (510) 985-3950; Fax: (510) 985-3101; Email: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34516

VASCULAR BIOLOGY: What AM I? AM is a regulator of vascular system functionality