Hypertensive encephalopathy and the blood-brain barrier: is deltaPKC a gatekeeper?
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.
Chou
Wen-Hai
WH
Ernest Gallo Clinic and Research Center, Department of Neurology, UCSF, Emeryville, California 94608, USA.
Messing
Robert O
RO
D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D020343:Hypertensive Encephalopathy / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000201:enzymology / Q000473:pathology
D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; C477270:Ser-Phe-Asn-Ser-Tyr-Glu-Leu-Gly-Glu-Ser-Leu; C497260:Prkcd protein, rat; D051745:Protein Kinase C-delta