title: Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB.
abstract: BACKGROUND
  As a complex nervous system disease, migraine causes severe healthy and social issues worldwide. Valproate (VPA) is a widely used treatment agent against seizures and bipolar disorder, and its function to alleviate damage due to migraine has also been verified in clinical investigations. However, the mechanism underlying the protective effect of VPA against migraine remains poorly revealed. In the current study, the major purpose was to uncover the mechanism which drove VPA to antagonize migraine.
  
  
  METHODS
  Nitroglycerin (NTG) was employed to induce a migraine model in rats and the migraine animals were exposed to treatment of VPA of different doses. Thereafter, the levels of indicators related to oxidative stress were measured and used to evaluate the anti-oxidant potential of VPA. The expression of calcitonin gene-related peptide (CGRP) and c-Fos was also quantified with ELISA and immunohistochemistry, respectively. Western blotting and electrophoretic mobility shift assays (EMSA) were conducted to explore the effect of VPA treatment on NF-кB pathway.
  
  
  RESULTS
  NTG induced the activation of oxidative stress and led to migraine in model animals, but pre-treatment with VPA attenuated the damage due to migraine attack in brain tissues. The level of lipid peroxidation was significantly reduced while the prodcution of anti-oxidant factors was restored. Furthermore, expressions of CGRP and c-Fos, which represented the neuronal activation, were also down-regulated by VPA. The results of western blotting and EMSA demonstrated that the above mentioned effect of VPA acted through the inhibition of NF-кB pathway.
  
  
  CONCLUSIONS
  Although controversies on the effect of VPA on NF-кB pathway existed, our study revealed an alternative mechanism of VPA in protecting against migraine, which would promote the development of therapeutic strategies of migraine.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Qi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Lian
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, 150001, People's Republic of China. zhongl_zhang67@sina.com.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D005996:Nitroglycerin; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D014635:Valproic Acid; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide
keywords: Anti-oxidant; Migraine; NF-кB; Nitroglycerin; Valparoate