Abstract
BackgroundAs 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.MethodsNitroglycerin (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.ResultsNTG 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.ConclusionsAlthough 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.
Highlights
As a complex nervous system disease, migraine causes severe healthy and social issues worldwide
The genes related to nitric oxide (NO) pathway, including genes encoding endothelial NO synthase, inducible NO synthase, and vascular endothelial growth factor (VEGF) all increased patients’ susceptibility to migraine [3]
MDA was representative of the lipid peroxidation and the level was up-regulated by NTG injection, indicating an increase in the lipid peroxidation in brain tissues
Summary
As a complex nervous system disease, migraine causes severe healthy and social issues worldwide. The mechanism underlying the protective effect of VPA against migraine remains poorly revealed. The major purpose was to uncover the mechanism which drove VPA to antagonize migraine. As a complicated nervous system disease, migraine is characterized by the disability of components in the trigeminal pain pathway. Patients with migraine are attacked by disabling headache associated with sensitivity to afferent inputs, including gastrointestinal inputs, light, sound, and head movement [1]. Based on the investigation in 2002, over 20 % of the world population are affected by migraine at some stage of their entire lives [2], casting severe healthy and social issues to the public health. The pathways involved in the induction of migraine by NO may depend on the activation of NF-кB [7], associated with the up-regulation of some
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