Migraine preventive drugs differentially affect cortical spreading depression in rat
Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of t...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110003487 |
| _version_ | 1830140315921547264 |
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| author | Volodymyr Borysovych Bogdanov Sylvie Multon Virginie Chauvel Olena Viktorivna Bogdanova Dimiter Prodanov Mykola Yukhymovych Makarchuk Jean Schoenen |
| author_facet | Volodymyr Borysovych Bogdanov Sylvie Multon Virginie Chauvel Olena Viktorivna Bogdanova Dimiter Prodanov Mykola Yukhymovych Makarchuk Jean Schoenen |
| author_sort | Volodymyr Borysovych Bogdanov |
| collection | DOAJ |
| description | Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2 h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura. |
| first_indexed | 2024-12-17T09:00:16Z |
| format | Article |
| id | doaj.art-3fe4a3d0d7f144bfa51c879aa3989a6c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T09:00:16Z |
| publishDate | 2011-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-3fe4a3d0d7f144bfa51c879aa3989a6c2022-12-21T21:55:45ZengElsevierNeurobiology of Disease1095-953X2011-02-01412430435Migraine preventive drugs differentially affect cortical spreading depression in ratVolodymyr Borysovych Bogdanov0Sylvie Multon1Virginie Chauvel2Olena Viktorivna Bogdanova3Dimiter Prodanov4Mykola Yukhymovych Makarchuk5Jean Schoenen6Headache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, Belgium; Human and Animal Physiology Department, Biological Faculty, Taras Shevchenko National University of Kyiv, Volodymyrska St., 64, 01033, Kyiv, UkraineHeadache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, BelgiumHeadache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, BelgiumHeadache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, Belgium; Biochemistry department, Biological Faculty, Taras Shevchenko National University of Kyiv, Volodymyrska St., 64, 01033, Kyiv, UkraineHeadache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, BelgiumHuman and Animal Physiology Department, Biological Faculty, Taras Shevchenko National University of Kyiv, Volodymyrska St., 64, 01033, Kyiv, UkraineHeadache Research Unit, GIGA-Neurosciences and Department of Neurology, Liège University, CHU Sart Tilman B36, T4, +1, B-4000, Liège, Belgium; Corresponding author. GIGA-Neurosciences, Cephalic Pain Research Unit, CHU Sart Tilman B36, T4, +1, B-4000 LIEGE, Belgium. Fax: +32 43665199, +32 42256451.Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2 h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura.http://www.sciencedirect.com/science/article/pii/S0969996110003487Cortical spreading depressionMigraineLamotrigineRiboflavinValproate |
| spellingShingle | Volodymyr Borysovych Bogdanov Sylvie Multon Virginie Chauvel Olena Viktorivna Bogdanova Dimiter Prodanov Mykola Yukhymovych Makarchuk Jean Schoenen Migraine preventive drugs differentially affect cortical spreading depression in rat Neurobiology of Disease Cortical spreading depression Migraine Lamotrigine Riboflavin Valproate |
| title | Migraine preventive drugs differentially affect cortical spreading depression in rat |
| title_full | Migraine preventive drugs differentially affect cortical spreading depression in rat |
| title_fullStr | Migraine preventive drugs differentially affect cortical spreading depression in rat |
| title_full_unstemmed | Migraine preventive drugs differentially affect cortical spreading depression in rat |
| title_short | Migraine preventive drugs differentially affect cortical spreading depression in rat |
| title_sort | migraine preventive drugs differentially affect cortical spreading depression in rat |
| topic | Cortical spreading depression Migraine Lamotrigine Riboflavin Valproate |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110003487 |
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