Brain, Vol. 125, No. 1, 102-112,
January 1, 2002
© 2002 Oxford University Press
Endothelin-1 potently induces Leão’s cortical spreading depression in vivo in the rat
A model for an endothelial trigger of migrainous aura?
Departments of 1Experimental Neurology, 2Neurology and 4Neurophysiology, Charité, Humboldt-University and 3Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Hospital, Free University of Berlin, Berlin, Germany Correspondence to: Jens P. Dreier, Department of Neurology, Charité, Humboldt Universität, Schumannstr. 20/21, 10117 Berlin, Germany E-mail: jens.dreier{at}charite.de
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 µM, 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. E. Tietjen, N. A. Herial, L. White, C. Utley, J. M. Kosmyna, and S. A. Khuder Migraine and Biomarkers of Endothelial Activation in Young Women Stroke, September 1, 2009; 40(9): 2977 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Rogawski Common Mechanisms in Migraine and Epilepsy: A Comment--Reply Arch Neurol, November 1, 2008; 65(11): 1546 - 1547. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Hansen, L. L. Thomsen, J. Olesen, and M. Ashina Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype Neurology, September 9, 2008; 71(11): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Strong, P. J. Anderson, H. R. Watts, D. J. Virley, A. Lloyd, E. A. Irving, T. Nagafuji, M. Ninomiya, H. Nakamura, A. K. Dunn, et al. Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex Brain, April 1, 2007; 130(4): 995 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hermans, M. C Post, V. Thijs, M. Spaepen, and W. I H L Budts Increased prevalence of migraine in adult congenital heart disease Heart, March 1, 2007; 93(3): 361 - 362. [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Dreier, J. Kleeberg, M. Alam, S. Major, M. Kohl-Bareis, G. C. Petzold, I. Victorov, U. Dirnagl, T. P. Obrenovitch, and J. Priller Endothelin-1-Induced Spreading Depression in Rats Is Associated with a Microarea of Selective Neuronal Necrosis Experimental Biology and Medicine, February 1, 2007; 232(2): 204 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kann and R. Kovacs Mitochondria and neuronal activity Am J Physiol Cell Physiol, February 1, 2007; 292(2): C641 - C657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kleeberg, G. C. Petzold, S. Major, U. Dirnagl, and J. P. Dreier ET-1 induces cortical spreading depression via activation of the ETA receptor/phospholipase C pathway in vivo Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1339 - H1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Kruit, M. A. van Buchem, P. A. M. Hofman, J. T. N. Bakkers, G. M. Terwindt, M. D. Ferrari, and L. J. Launer Migraine as a Risk Factor for Subclinical Brain Lesions JAMA, January 28, 2004; 291(4): 427 - 434. [Abstract] [Full Text] [PDF]
|
|