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The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice

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Abstract

There have been conflicting reports regarding the role of ethanol in seizure. Another effect of ethanol is vascular damage in cerebral tissue. This study investigates the influence of ethanol on antiepileptic efficacy of valproic acid (VPA) and cerebral microvascular structure. In this study, four groups of mice (25–30 g) received pentylenetetrazole (PTZ) i.p. (37 mg/kg) every other day. Different groups of animals received an injection of saline, ethanol (1 g/kg), VPA (100 mg/kg), or VPA and ethanol 30 min before PTZ. Animals in groups 5 and 6 received only ethanol and saline, respectively. After recording seizure parameters, the animals were sacrificed under deep anesthesia and the brains of the animals were removed and fixed, thereafter coronal sections were prepared from cerebral cortex. Then, the cerebral microvessels were counted in microscopic sections after hematoxylin–eosin staining. Ethanol injection (1 g/kg) for 7 days decreased stage 4 duration and increased latency to the onset of stage 1 and stage 4 of seizure (p < 0.001). Concomitant injection of VPA (5 min before ethanol) and ethanol had significantly stronger anticonvulsant effects than VPA alone (p < 0.001). Furthermore, the findings showed that not only the cerebral microvessels increased significantly in ethanol group compared with saline group (p < 0.05), but also there were morphological changes in vascular endothelium in ethanol group. The obtained results show that short-term ethanol administration has anticonvulsant effects along with VPA, and enhances the anticonvulsant effects of VPA. Furthermore, it is possible that VPA leads to decreased ethanol-induced vascular damage.

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Authors and Affiliations

  1. Department of Anatomy, Cellular and Molecular Research Center, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Rahim Golmohammadi

  2. Department of Physiology, Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Akbar Pejhan & Mohammad Mohammad-Zadeh

  3. Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

    Hassan Azhdari-Zarmehri

Authors
  1. Rahim Golmohammadi
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  2. Akbar Pejhan
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  3. Hassan Azhdari-Zarmehri
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  4. Mohammad Mohammad-Zadeh
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Correspondence to Mohammad Mohammad-Zadeh.

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Golmohammadi, R., Pejhan, A., Azhdari-Zarmehri, H. et al. The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice. Neurol Sci 34, 1125–1131 (2013). https://doi.org/10.1007/s10072-012-1190-y

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  • DOI: https://doi.org/10.1007/s10072-012-1190-y

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