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

J Clin Invest. 2008 Jan;118(1):17-20. doi: 10.1172/JCI34516.

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 deltaPKC, they stabilized the BBB and improved mortality in hypertensive rats. This study highlights the therapeutic potential of deltaPKC inhibitors in hypertensive encephalopathy and provides incentive to elucidate deltaPKC signaling pathways that mediate BBB dysfunction in other disease states.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / enzymology*
  • Blood-Brain Barrier / pathology
  • Brain Edema / drug therapy
  • Brain Edema / enzymology
  • Brain Edema / pathology
  • Capillary Permeability / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / pathology
  • Hypertensive Encephalopathy / drug therapy*
  • Hypertensive Encephalopathy / enzymology
  • Hypertensive Encephalopathy / pathology
  • Male
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / therapeutic use*
  • Protein Kinase C-delta / antagonists & inhibitors*
  • Protein Kinase C-delta / metabolism
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Rats
  • Rats, Inbred Dahl
  • Rats, Sprague-Dawley
  • Tight Junctions / enzymology
  • Tight Junctions / pathology

Substances

  • Oligopeptides
  • Protein Kinase Inhibitors
  • Ser-Phe-Asn-Ser-Tyr-Glu-Leu-Gly-Glu-Ser-Leu
  • Prkcd protein, rat
  • Protein Kinase C-delta