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

ABSTRACT 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.