Research Article


DOI :10.26650/EurJBiol.2018.0015   IUP :10.26650/EurJBiol.2018.0015    Full Text (PDF)

The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats

Ahmet Can HiçyılmazKadriye Akgün Dar

Objective: Migraine is one of the common primary headaches which affects the majority of the population. However, in spite of increasing information on migraine pathophysiology and various researches, the underlying mechanisms of migraine attacks still not completely understood. Statins have antioxidant, anti-inflammatory neuroprotective effects and they might be a useful drug for curing neurodegenerative disorders. There are several studies suggesting nitric oxide (NO) causes migraine attacks in migraine pathogenesis. We aimed to investigate the effects of atorvastatin (AT) which is a member of the statin family, on migraine pathophysiology in ovariectomized female rats in which migraine was stimulated using nitroglycerine (NTG). Materials and Methods: In the study, ovariectomized adult Sprague Dawley female rats were divided into 4 groups; control, NTG, AT, NTG+AT. We examined immunohistochemically inducible nitric oxide (iNOS), endothelial nitric oxide (eNOS), neuronal nitric oxide (nNOS), matrix metalloproteinase-2 (MMP-2), β-catenin expression on brain sections and biochemically c-fos, calcitonin gene-related peptide (CGRP), β-catenin, calcium-binding protein B (S100B), NO, total antioxidant capacity (TAS) and total oxidant capacity (TOS) levels. Results: Our results showed that AT was immunohistochemically increasing eNOS and nNOS levels, and reducing iNOS. In brain homogenates AT was reducing S100B, CGRP, c-fos, total Nitrite-Nitrate, β-catenin but increasing TAS and TOS. There was no change in MMP-2. Also, our findings showed that AT could inhibit astroglial activity with its anti-inflammatory effect and showed a protective effect towards blood-brain barrier and reduced the risk of possible neurodegenerative diseases in rats with migraine. Conclusion: Our findings showed that AT could inhibit astroglial activity with its anti-inflammatory effect and showed a protective effect towards blood-brain barrier and reduced the risk of possible neurodegenerative diseases in rats with migraine. Our results will provide a significant contribution to studies in this field.

PDF View

References

  • 1. Erdener SE, Dalkara T. Modelling headache and migraine and its pharmacological manipulation. Br J Pharmacol 2014; 171(20): 4575-94. google scholar
  • 2. Fischer M, Wille G, Klien S, Shanib H, Holle D, Gaul C, et al. Brainderived neurotrophic factor in primary headaches. J Headache Pain 2012; 13(6): 469-75. google scholar
  • 3. Somerville BW. Estrogen-withdrawal migraine. I. Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration. Neurology 1975; 25(3): 239–44. google scholar
  • 4. Multon S, Pardutz A, Mosen J, Hua MT, Defays C, Honda S, et al. Lack of estrogen increases pain in the trigeminal formalin model: a behavioural and immunocytochemical study of transgenic ArKO mice. Pain 2005; 114(1-2): 257-65. google scholar
  • 5. Scharfman HE, MacLusky NJ. Estrogen-growth factor interactions and their contributions to neurological disorders. Headache 2008; 48 Suppl 2: S77-89. google scholar
  • 6. Merki-Feld GS, Imthurn B, Langner R, Seifert B, Gantenbein AR. Positive effects of the progestin desogestrel 75 μg on migraine frequency and use of acute medication are sustained over a treatment period of 180 days. J Headache Pain 2015; 16: 522. google scholar
  • 7. Goldstein LB. Statins and ischemic stroke severity: cytoprotection. Current Atherosclerosis Reports 2009; 11(4): 296-300. google scholar
  • 8. Hasanein P, Shahidi S. Effects of combined treatment with vitamins C and E on passive avoidance learning and memory in diabetic rats. Neurobiology of Learning and Memory 2010; 93(4): 472-8. google scholar
  • 9. Üzüm G, Akgün-Dar K, Aksu A. The effects of atorvastatin on the development of Pentylenetetrazole induced kindling, related learning and memory impairments. Epilepsy & Behavior 2010; 19 (3): 284-289. google scholar
  • 10. Akgün-Dar K, Kapucu A, Acar S, Üzüm G. Evaluation of Antiepileptogenic Effect of Atorvastatin on Development of Pentylenetetrazole Induced Kindling in Rats: The Responsibility of Inducible Nitric Oxide Synthase and Metalloproteinase 2. Turkiye Klinikleri J Med Sci 2013; 33: 995-1006. google scholar
  • 11. Bahçekapılı N, Akgün-Dar K, Albeniz I, Kapucu A, Kandil A, Yağız O, et al. Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole induced generalized seizures. Int J Neurosci 2014; 124(10): 762-70. google scholar
  • 12. Yin Z, Fang Y, Ren L, Wang X, Zhang A, Lin J, et al. Atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a rat model of migraine. Neurosci Lett 2009; 465(1): 61-5. google scholar
  • 13. Sarrouilhe D, Dejean C, Mesnil M. Involvement of gap junction channels in the pathophysiology of migraine with aura. Front Physiol 2014; 5: 78. google scholar
  • 14. Sicuteri F, Del Bene E, Poggioni M, Bonazzi A. Unmasking latent dysnociception in healthy subjects. Headache 1987; 27(4): 180-5. google scholar
  • 15. Olesen J, Iversen HK, Thomsen LL. Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain. Neuroreport 1993; 4(8): 1027-30. google scholar
  • 16. Pardutz A, Krizbai I, Multon S, Vecsei L, Schoenen J. Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis. Neuroreport 2000; 11(14): 3071-5. google scholar
  • 17. Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache. Pain 1995; 62(2): 129-39. google scholar
  • 18. Silberstein SD, Merriam GR. Physiology of the menstrual cycle. Cephalalgia 2000; 20(3): 148-54. google scholar
  • 19. Tassorelli C, Joseph SA. Systemic nitroglycerin induces Fos immunoreactivity in brainstem and forebrain structures of the rat. Brain Res 1995; 682(1-2): 167-81. google scholar
  • 20. Garry MG, Walton LP, Davis MA. Capsaicin-evoked release of immunoreactive calcitonin gene-related peptide from the spinal cord is mediated by nitric oxide but not by cyclic GMP. Brain Res 2000; 861(2): 208-19. google scholar
  • 21. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990; 28(2): 183-7. google scholar
  • 22. Greco R, Tassorelli C, Mangione AS, Smeraldi A, Allena M, Sandrini G, et al. Effect of sex and estrogens on neuronal activation in an animal model of migraine. Headache 2013; 53(2): 288-96. google scholar
  • 23. Arakaki X, Galbraith G, Pikov V, Fonteh AN, Harrington MG. Altered brainstem auditory evoked potentials in a rat central sensitization model are similiar to those in migraine. Brain Res 2014; 1563: 110-21. google scholar
  • 24. Mrak E, Guidobono F, Moro G, Fraschini G, Rubinacci A, Villa I. Calcitonin gene-related peptide (CGRP) inhibits apoptosis in human osteoblasts by β-catenin stabilization. J Cell Physiol 2010; 225(3): 701-8. google scholar
  • 25. Prévotat L, Filomenko R, Solary E, Jeannin JF, Bettaieb A. Nitric oxide-induced down-regulation of beta-catenin in colon cancer cells by a proteasome-independent specific pathway. Gastroenterology 2006; 131(4): 1142-52. 26. Wang Z, Xu L, Zhu X, Cui W, Sun Y, Nishijo H, et al. Demethylation of specific Wnt/β-catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure. Anat Rec (Hoboken) 2010; 293(11): 1947-53. google scholar
  • 27. Wang PH, Zhao LX, Wan JY, Zhang L, Mao XN, Long FY, et al. Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent. Fitoterapia 2016; Mar; 109: 52-7. google scholar
  • 28. Offenhauser N, Zinck T, Hoffmann J, Schiemann K, Schuh-Hofer S, Rohde W, et al. CGRP release and c-fos expression within trigeminal nucleus caudalis of the rat following glyceryltrinitrate infusion. Cephalalgia 2005; 25(3): 225-36. google scholar
  • 29. Tassorelli R, Greco P, Morazzoni A, Riva G, Sandrini G, Nappi G. Parthenolide is the component of tanacetum parthenium that inhibits nitroglycerin-induced Fos activation: studies in an animal model of migraine. Cephalalgia 2005; 25(8): 612-21. google scholar
  • 30. Knyihár-Csillik E, Toldi J, Mihály A, Krisztin-Péva B, Chadaide Z, Németh H, et al. Kynurenine in combination with probenecid mitigates the stimulation-induced increase of c-fos immunoreactivity of the rat caudal trigeminal nucleus in an experimental migraine model. J Neural Transm (Vienna) 2007; 114(4): 417-21. google scholar
  • 31. Zhu X, Han Y, Xiong W, Liu W, Lu S, Li J, et al. Effects of heating coagulation of middle meningeal artery on plasma CGRP level and c-fos expression in migraine rat triggered by nitroglycerin. Neurol Sci 2011; 32(4): 589-94. google scholar
  • 32. Teepker M, Munk K, Mylius V, Haag A, Möller JC, Oertel WH, et al. Serum concentrations of s100b and NSE in migraine. Headache 2009; 49(2): 245-52. google scholar
  • 33. Yilmaz N, Karaali K, Ozdem S, Turkay M, Unal A, Dora B. Elevated S100B and neuron specific enolase levels in patients with migraine-without aura: evidence for neurodegeneration? Cell Mol Neurobiol 2011; 31(4): 579-85. google scholar
  • 34. Steinacker P, Weidehaas K, Cepek L, Feneberg E, Kretzschmar HA, Otto M. Influence of the blood-CSF-barrier function on S100B in neurodegenerative diseases. Acta Neurol Scand 2013; 128(4): 249-56. google scholar
  • 35. Eren Y, Dirik E, Neşelioğlu S, Erel Ö. Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study. Acta Neurol Belg 2015; 115(4): 643-9. google scholar
  • 36. Yilmaz N, Aydin O, Yegin A, Tiltak A, Eren E. Increased levels of total oxidant status and decreased activity of arylesterase in migraineurs. Clin Biochem 2011; 44(10-11): 832-7. google scholar
  • 37. Alp R, Selek S, Alp SI, Taşkin A, Koçyiğit A. Oxidative and antioxidative balance in patients of migraine. Eur Rev Med Pharmacol Sci 2010; 14(10): 877-82. 38. Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res 2000; 87(8): 670-6. google scholar
  • 39. Wang Q, Yan J, Chen X, Li J, Yang Y, Weng J, et al. Statins: multiple neuroprotective mechanisms in neurodegenerative diseases. Exp Neurol 2011; 230(1): 27-34. google scholar
  • 40. Eroğlu F, Eroğlu HE. Ratlarda Analjezi ve Anestezi, Küçük Deney Hayvanlarından Rat. In: Yücel O. (ed.), JCAM, Matris Tanıtım Baskı Hizmetleri Hilal Mahallesi (Yıldız) 4. Cadde, 701. Sokak, No: 20/A 06550 Çankaya, Ankara, Türkiye, 2012; ISBN: 978-605-87501-2-8, 52-59. google scholar
  • 41. Jagatic J, Weiskopf R. A fluorescent method for staining mast cells. Arch Pathol 1966; 82(5): 430-3. google scholar
  • 42. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004; 37(2): 112-9. google scholar
  • 43. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005 38(12): 1103-11. google scholar
  • 44. Özyiğit F. Nöropatik Farelerde Oluşan Mekanik Allodini Ve Hiperaljezi Üzerine Minosiklin’in Tek Başına Ve Morfin İle Birlikte Kullanıldığındaki Etkisi. T.C. Trakya Üniversitesi Tıp Fakültesi Farmakoloji Ana Bilim Dalı, Yüksek Lisans Tezi, 2007. google scholar
  • 45. Akerman S, Holland PR, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci 2011; 12(10): 570-84. google scholar
  • 46. Greco R, Tassorelli C, Cappelletti D, Sandrini G, Nappi G. Activation of the transcription factor NF-kappaB in the nucleus trigeminalis caudalis in an animal model of migraine. Neurotoxicology 2005; 26(5): 795-800. google scholar
  • 47. Pardutz A, Szatmári E, Vecsei L, Schoenen J. Nitroglycerin-induced nNOS increase in rat trigeminal nucleus caudalis is inhibited by systemic administration of lysine acetylsalicylate but not of sumatriptan. Cephalalgia 2004; 24(6): 439-45. google scholar
  • 48. Suwattanasophon C, Phansuwan-Pujito P, Srikiatkhachorn A. 5-HT(1B/1D) serotonin receptor agonist attenuates nitroglycerinevoked nitric oxide synthase expression in trigeminal pathway. Cephalalgia 2003; 23(8): 825-32. google scholar
  • 49. Pardutz A, Krizbai I, Multon S, Vecsei L, Schoenen J. Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis. Neuroreport 2000; 11(14): 3071-5. google scholar
  • 50. Varga H, Pardutz A, Vamos E, Plangar I, Egyud E, Tajti J, et al. Cox2 inhibitor attenuates NO-induced nNOS in rat caudal trigeminal nucleus. Headache 2007; 47(9): 1319-25. google scholar
  • 51. Pardutz A, Hoyk Z, Varga H, Vecsei L, Schoenen J. Oestrogenmodulated increase of calmodulin-dependent protein kinase II (CamKII) in rat spinal trigeminal nucleus after systemic nitroglycerin. Cephalalgia 2007; 27(1): 46-53. google scholar
  • 52. Yin Z, Fang Y, Ren L, Wang X, Zhang A, Lin J, Li X. Atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a rat model of migraine. Neurosci Lett 2009; 465(1): 61-5. google scholar
  • 53. Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A. Characterization of a novel model of chronic migraine. Pain 2014; 155(2): 269-74. google scholar
  • 54. Iversen HK, Olesen J, Tfelt-hansen P. Intravenous nitroglycerin as an experimental-model of vascular headache basic characteristics. Pain 1989; 38(1): 17-24. google scholar
  • 55. Olesen J, Thomsen LL, Iversen H. Nitric oxide is a key molecule in migraine and other vascular headaches. Trends Pharmacol Sci 1994; 15(5): 149-53. google scholar
  • 56. Capuano A, De Corato A, Lisi L, Tringali G, Navarra P, Dello Russo C. Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology. Mol Pain 2009; 5: 43. google scholar
  • 57. Villalón CM, Olesen J. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Ther 2009; 124(3): 309-23. google scholar
  • 58. Kuzawińska O, Lis K, Cudna A, Bałkowiec-Iskra E. Gender differences in the neurochemical response of trigeminal ganglion neurons to peripheral inflammation in mice. Acta Neurobiol Exp (Wars) 2014; 74(2): 227-32. google scholar
  • 59. Ward TN. Migraine diagnosis and pathophysiology. Continuum (Minneap Minn) 2012; 18(4): 753-63. google scholar
  • 60. Sarrouilhe D, Dejean C, Mesnil M. Involvement of gap junction channels in the pathophysiology of migraine with aura. Front Physiol 2014; 5: 78. google scholar
  • 61. Ji Y, Murphy AZ, Traub RJ. Estrogen modulates the visceromotor reflex and responses of spinal dorsal horn neurons to colorectal stimulation in the rat. J Neurosci 2003; 23(9): 3908-15. google scholar
  • 62. Sachs M, Pape HC, Speckmann EJ, Gorji A. The effect of estrogen and progesterone on spreading depression in rat neocortical tissues. Neurobiol Dis 2007; 25(1): 27-34. google scholar
  • 63. Peroni RN, Orliac ML, Abramoff T, Ribeiro ML, Franchi AM, AdlerGraschinsky E. Participation of CGRP and prostanoids in the sexlinked differences of vascular anandamide effects in mesenteric beds of Sprague-Dawley rats. Eur J Pharmacol 2007; 557(1): 49-57. google scholar
  • 64. Wrobel Goldberg S, Silberstein SD. Targeting CGRP: A New Era for Migraine Treatment. CNS Drugs 2015; 29(6): 443-52. google scholar
  • 65. Messlinger K, Lennerz JK, Eberhardt M, Fischer MJ. CGRP and NO in the trigeminal system: mechanisms and role in headache generation. Headache 2012; 52(9): 1411-27. google scholar
  • 66. Mitsikostas DD, Sanchez del Rio M. Receptor systems mediating cfos expression within trigeminal nucleus caudalis in animal models of migraine. Brain Res Brain Res Rev 2001; 35(1): 20-35. google scholar
  • 67. Greco R, Tassorelli C, Cappelletti D, Sandrini G, Nappi G. Activation of the transcription factor NF-kappaB in the nucleus trigeminalis caudalis in an animal model of migraine. Neurotoxicology 2005; 26(5): 795-800. google scholar
  • 68. Zhang X, Kainz V, Zhao J, Strassman AM, Levy D. Vascular extracellular signal-regulated kinase mediates migraine-related sensitization of meningeal nociceptors. Ann Neurol 2013; 73(6): 741-50. google scholar
  • 69. Chenn A, Walsh CA. Increased neuronal production, enlarged forebrains and cytoarchitectural distortions in beta-catenin overexpressing transgenic mice. Cereb Cortex 2003; 13(6): 599-606. google scholar
  • 70. Yang J, Zhang X, Wu Y, Zhao B, Liu X, Pan Y, et al. Wnt/β-catenin signaling mediates the seizure-facilitating effect of postischemic reactive astrocytes after pentylenetetrazole-kindling. Glia 2016; 64(6):1083-91. google scholar
  • 71. Siva A, Murat H. editors, Baş Ağrısı Epidemiyolojisi, İ.Ü. Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri. Baş, Boyun, Bel Ağrıları. Siva A 2002; 30, 9-14. google scholar
  • 72. Sarrouilhe D, Dejean C, Mesnil M. Involvement of gap junction channels in the pathophysiology of migraine with aura. Front Physiol 2014; 5: 78. google scholar
  • 73. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets 2011; 10(7): 808-19. google scholar
  • 74. Reiss AB, Wirkowski E. Statins in neurological disorders: mechanisms and therapeutic value. ScientificWorldJournal 2009; 9: 1242-59. google scholar
  • 75. Kampoli AM, Tousoulis D, Tentolouris C, Stefanadis C. Novel agents targeting nitric oxide. Curr Vasc Pharmacol 2012; 10(1): 61-76. google scholar
  • 76. Banach M, Czuczwar SJ, Borowicz KK. Statins - are they anticonvulsant? Pharmacol Rep 2014; 66(4): 521-8. google scholar
  • 77. Schmidt HH, Walter U. NO at work. Cell 1994; 78(6): 919-25. 78. Rikitake Y, Liao JK. Rho GTPases, statins, and nitric oxide. Circ Res 2005; 97(12): 1232-5. google scholar
  • 79. Sarrouilhe D, Dejean C, Mesnil M. Involvement of gap junction channels in the pathophysiology of migraine with aura. Front Physiol 2014; 5: 78. google scholar
  • 80. Yin Z, Fang Y, Ren L, Wang X, Zhang A, Lin J, et al. Atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a rat model of migraine. Neurosci Lett 2009; 465(1): 61-5. google scholar
  • 81. Brandes JL. The influence on migraine: A systematic review. JAMA 2006; 295(15): 1824-30. google scholar
  • 82. Bereiter DA, Cioffi JL, Bereiter DF. Oestrogen receptorimmunoreactive neurons in the trigeminal sensory system of male and cycling female rats. Arch Oral Biol 2005; 50(11): 971-9. 83. Marcus DA. Estrogen and tension-type headache. Curr Pain Headache Rep 2001; 5(5): 449-53. google scholar
  • 84. Shimomura T, Murakami F, Kotani K, Ikawa S, Kono S. Platelet nitric oxide metabolites in migraine. Cephalalgia 1999; 19(4): 218-22. google scholar
  • 85. D’Amico D, Ferraris A, Leone M, Catania A, Carlin A, Grazzi I, et al. Increased plasma nitrites in migraine and cluster headache patients in interictal period: basal hyperactivity of L-arginine NO patway? Cephalalgia 2002; 22(1): 33-6. google scholar
  • 86. Stirparo G, Zicari A, Favilla M, Lipari M, Martelletti M. Linked activation of nitric oxide synthase and cyclooxygenase in peripheral monocytes of asymptomatic mi graine without aura patients. Cephalalgia 2000; 20(2): 100-6. google scholar
  • 87. Gruber HJ, Bernecker C, Lechner A, Weiss S, Wallner-Blazek M, Meinitzer A, et al. Increased nitric oxide stress is associated with migraine. Cephalalgia 2010; 30(4): 486-92. google scholar
  • 88. Lucchesi C, Baldacci F, Cafalli M, Chico L, Lo Gerfo A, Bonuccelli U, et al. Evidences of reduced antioxidant activity in patients with chronic migraine and medication-overuse headache. Headache 2015; 55(7): 984-91. google scholar
  • 89. Berk M, Dean O, Drexhage H, McNeil JJ, Moylan S, O’Neil A, et al. Aspirin: A review of its neurobiological properties and therapeutic potential for mental illness. BMC Med 2013; 11: 74. google scholar
  • 90. Edvinsson L, Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia 2017; 0(0) 1–8 (333102417736900). google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Hiçyılmaz, A.C., & Akgün Dar, K. (2019). The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats. European Journal of Biology, 78(1), 11-22. https://doi.org/10.26650/EurJBiol.2018.0015


AMA

Hiçyılmaz A C, Akgün Dar K. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats. European Journal of Biology. 2019;78(1):11-22. https://doi.org/10.26650/EurJBiol.2018.0015


ABNT

Hiçyılmaz, A.C.; Akgün Dar, K. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats. European Journal of Biology, [Publisher Location], v. 78, n. 1, p. 11-22, 2019.


Chicago: Author-Date Style

Hiçyılmaz, Ahmet Can, and Kadriye Akgün Dar. 2019. “The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats.” European Journal of Biology 78, no. 1: 11-22. https://doi.org/10.26650/EurJBiol.2018.0015


Chicago: Humanities Style

Hiçyılmaz, Ahmet Can, and Kadriye Akgün Dar. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats.” European Journal of Biology 78, no. 1 (May. 2024): 11-22. https://doi.org/10.26650/EurJBiol.2018.0015


Harvard: Australian Style

Hiçyılmaz, AC & Akgün Dar, K 2019, 'The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats', European Journal of Biology, vol. 78, no. 1, pp. 11-22, viewed 19 May. 2024, https://doi.org/10.26650/EurJBiol.2018.0015


Harvard: Author-Date Style

Hiçyılmaz, A.C. and Akgün Dar, K. (2019) ‘The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats’, European Journal of Biology, 78(1), pp. 11-22. https://doi.org/10.26650/EurJBiol.2018.0015 (19 May. 2024).


MLA

Hiçyılmaz, Ahmet Can, and Kadriye Akgün Dar. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats.” European Journal of Biology, vol. 78, no. 1, 2019, pp. 11-22. [Database Container], https://doi.org/10.26650/EurJBiol.2018.0015


Vancouver

Hiçyılmaz AC, Akgün Dar K. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats. European Journal of Biology [Internet]. 19 May. 2024 [cited 19 May. 2024];78(1):11-22. Available from: https://doi.org/10.26650/EurJBiol.2018.0015 doi: 10.26650/EurJBiol.2018.0015


ISNAD

Hiçyılmaz, AhmetCan - Akgün Dar, Kadriye. The Effects of Atorvastatin on the Migraine Pathophysiology in Nitroglycerin Induced Migraine in Ovariectomized Rats”. European Journal of Biology 78/1 (May. 2024): 11-22. https://doi.org/10.26650/EurJBiol.2018.0015



TIMELINE


Submitted08.11.2018
Accepted06.02.2019
Published Online31.05.2019

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.