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Valproate (<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>) is used as an anti\u2010epilepsy drug in clinic. This study aimed to investigate the role of <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content> in nitroglycerin (<jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content>)\u2010induced migraine using a mouse model. <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content> was employed by intraperitoneal injection to induce a migraine model in mice. The <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content> administration caused mouse head discomforts, decreased tolerance to cold or hot stimulation and increased content of nitric oxide, calcitonin gene\u2010related peptide and neuropeptide Y in serum, which were ameliorated by intraperitoneal injection of <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>. The levels of two inflammatory factors, interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2 and inducible nitric oxide synthase, in dura mater were increased by <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content> treatment, while the increase was attenuated by application of <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>. In addition, the phosphorylation levels of protein kinase C (<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>) \u03b1, \u03b3, \u03b4 and \u03b5 were increased by <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content> and decreased by <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>. However, their total expression at the transcriptional and translational levels did not change significantly. Two substrates of <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> cAMP<\/jats:styled-content>\u2010response element binding protein 1 and signal transducer and activator of transcription 1 were also phosphorylated by <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content> application, and the phosphorylation level was attenuated by <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>, consistent with the change of <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> informs. Together, we demonstrated that <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content> prevented damage due to migraine by inhibiting <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> signalling in <jats:styled-content style=\"fixed-case\">NTG<\/jats:styled-content>\u2010injected mice, which may provide a basis for investigating the clinical treatment of migraine.<\/jats:p>","DOI":"10.1111\/bcpt.12915","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T02:02:43Z","timestamp":1507514563000},"page":"310-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Valproate Plays a Protective Role against Migraine by Inhibiting Protein Kinase C Signalling in Nitroglycerin\u2010treated Mice"],"prefix":"10.1111","volume":"122","author":[{"given":"Lian","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital 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