Cortical glutamate and gamma-aminobutyric acid over the course of a provoked migraine attack, a 7 Tesla magnetic resonance spectroscopy study
Onderwater, Gerrit L.J.; Wijnen, Jannie P.; Najac, Chloé; van Dongen, Robin M.; Ronen, Itamar; Webb, Andrew; Zielman, Ronald; van Zwet, Erik W.; Ferrari, Michel D.; Kan, Hermien E.; Kruit, Mark C.; Terwindt, Gisela M.
(2021) NeuroImage: Clinical, volume 32, pp. 1 - 11
(Article)
Abstract
Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura
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and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single-volume proton magnetic resonance spectra (1H–MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack.
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Keywords: GABA, Glutamate, Glyceryl trinitrate, Magnetic resonance spectroscopy, Migraine, Glutamic Acid, gamma-Aminobutyric Acid, Magnetic Resonance Spectroscopy, Humans, Migraine Disorders/diagnostic imaging, Nitroglycerin, Female, Clinical Neurology, Neurology, Cognitive Neuroscience, Radiology Nuclear Medicine and imaging, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 2213-1582
Publisher: Elsevier BV
Note: Funding Information: A.G. Webb reports independent support from Dutch Research Council (NWO) and the European Research Council. M.D. Ferrari reports grants and consultancy or industry support from Medtronic, Novartis, Amgen, Lilly, Teva, electroCore and independent support from Dutch Research Council , NIH, European Community, and the Dutch Heart Foundation. H.E. Kan reports independent grants from NWO, Duchenne Parent Project, and the EU, consultancy for PTC therapeutics and trial support from ImagingDMD outside the submitted work. R. Zielman reports support for conference visits from Menarini and Allergan, and is currently an employee at Novartis. G.M. Terwindt reports grants or consultancy support from Novartis, Lilly, Teva, Allergan, and independent support from the Dutch Research Council (ZonMW) the Dutch Heart Foundation, and Dutch Brain Foundation. The other authors report no conflicts of interest. Funding Information: This study was supported by the Dutch Research Council (VICI grant 918.56.601 and Spinoza 2009 to MDF; Clinical Fellowship 90700217 and VIDI grant 917.11.31 to GMT), and European Research Council FP7-EUROHEADPAIN - no. 602633. Publisher Copyright: © 2021 The Author(s)
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