Endothelin-1 potently induces Leão's cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?

Details

Serval ID
serval:BIB_385D5EEBE43D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Endothelin-1 potently induces Leão's cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?
Journal
Brain
Author(s)
Dreier J.P., Kleeberg J., Petzold G., Priller J., Windmüller O., Orzechowski H.D., Lindauer U., Heinemann U., Einhäupl K.M., Dirnagl U.
ISSN
0006-8950 (Print)
ISSN-L
0006-8950
Publication state
Published
Issued date
01/2002
Peer-reviewed
Oui
Volume
125
Number
Pt 1
Pages
102-112
Language
english
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't
Abstract
According to the 'neuronal' theory, cortical spreading depression (CSD) is the pathophysiological correlate of migrainous aura. However, the 'vascular' theory has implicated altered vascular function in the induction of aura symptoms. The possibility of a vascular origin of aura symptoms is supported, e.g. by the clinical observation that cerebral angiography frequently provokes migrainous aura. This suggests that endothelial irritation may somehow initiate one of the pathways resulting in migrainous aura. Up to now, an endothelium-derived factor has never been shown to trigger CSD. Here, for the first time, we demonstrate and characterize the ability of the vasoconstrictor and astroglial/neuronal modulator endothelin-1 to trigger Leão's 'spreading depression of activity' in vivo in rats. At a concentration range between 10 nM and 1 microM, endothelin-1 induced changes characteristic of CSD with regard to the rate of propagation, steady (direct current) potential and extracellular K(+)-concentration. A spreading hyperaemia followed by oligaemia was observed similar to those in K(+)-induced CSD. Endothelin-1 did not provoke changes characteristic of a terminal depolarization. The mechanism by which endothelin-1 generated CSD involved the N-methyl-D-asparate receptor. Cerebral blood flow decreased slightly, but significantly, before endothelin-1 generated CSD. A vasodilator (NO*-donor) shifted the threshold for CSD induction to higher concentrations of endothelin-1. Endothelin-1, in contrast to K(+), did not induce CSD in rat brain slices suggesting indirectly that endothelin-1 may require intact perfusion to exert its effects. In conclusion, endothelin-1 was found in the experiment to be the most potent inducer of CSD currently known. We propose endothelin-1 as a possible candidate for the yet enigmatic link between endothelial irritation and migrainous aura.
Keywords
Animals, Cerebral Cortex/cytology, Cerebral Cortex/drug effects, Cerebrovascular Circulation/drug effects, Cortical Spreading Depression/drug effects, Cortical Spreading Depression/physiology, Dizocilpine Maleate/pharmacology, Electrophysiology, Endothelin-1/pharmacology, Humans, Laser-Doppler Flowmetry, Male, Migraine with Aura/etiology, Migraine with Aura/physiopathology, Models, Biological, Neuroglia/metabolism, Neurons/metabolism, Potassium/pharmacology, Rats, Rats, Wistar, Spermine/pharmacology, Vasoconstrictor Agents/pharmacology, Vasodilator Agents/pharmacology
Pubmed
Create date
03/10/2012 22:59
Last modification date
20/08/2019 13:27
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