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Hypertensive encephalopathy and the blood-brain barrier: is δPKC a gatekeeper?
Wen-Hai Chou, Robert O. Messing
Wen-Hai Chou, Robert O. Messing
Published December 20, 2007
Citation Information: J Clin Invest. 2008;118(1):17-20. https://doi.org/10.1172/JCI34516.
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Commentary

Hypertensive encephalopathy and the blood-brain barrier: is δPKC a gatekeeper?

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Abstract

Hypertensive encephalopathy is a life-threatening condition due to elevation of cerebral perfusion pressure beyond the limits of autoregulation. Breakdown of the blood-brain barrier (BBB) leads to cerebral edema and reduced blood flow. In this issue of the JCI, Mochly-Rosen and colleagues demonstrate a novel molecular strategy for preserving the BBB in a model of hypertension-induced encephalopathy (see the related article beginning on page 173). Using a rationally designed peptide inhibitor of δPKC, they stabilized the BBB and improved mortality in hypertensive rats. This study highlights the therapeutic potential of δPKC inhibitors in hypertensive encephalopathy and provides incentive to elucidate δPKC signaling pathways that mediate BBB dysfunction in other disease states.

Authors

Wen-Hai Chou, Robert O. Messing

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Figure 1

Structure of the BBB and tight junction.

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Structure of the BBB and tight junction.
(A) The BBB is formed in the ce...
(A) The BBB is formed in the central nervous system by capillary endothelial cells and surrounding perivascular elements (basal lamina, pericyte, astrocyte end-foot, and interneurons). (B) The tight junction is established by the interaction between the transmembrane proteins (claudins, occludin, and junction adhesion molecule) on adjacent endothelial cells. The C terminal of these transmembrane proteins is linked to cytoskeletal actin through ZO-1. In response to pathological stimuli, δPKC may directly or indirectly increase phosphorylation of ZO-1, thus disrupting the association between ZO-1 and the actin cytoskeleton. The disorganization of proteins at the tight junction may result in the aberrant permeability of the BBB.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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