Vitamin D receptor activation influences the ERK pathway and protects against neurological deficits and neuronal death

Yuan,Jie; Guo,Xin; Liu,Zhengang; Zhao,Xiuqin; Feng,Yan; Song,Sixin; Cui,Changmeng; Jiang,Pei

doi:10.3892/ijmm.2017.3249

Vitamin D receptor activation influences the ERK pathway and protects against neurological deficits and neuronal death

Authors:
- Jie Yuan
- Xin Guo
- Zhengang Liu
- Xiuqin Zhao
- Yan Feng
- Sixin Song
- Changmeng Cui
- Pei Jiang
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Affiliations: Department of Neurology, Institute of Mental Health, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Neurology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Neurology, Weixian People's Hospital, Xingtai, Hebei 054700, P.R. China, Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Neurosurgery, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, P.R. China, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China, Department of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, Shandong 272000, P.R. China
Published online on: November 9, 2017 https://doi.org/10.3892/ijmm.2017.3249
Pages: 364-372
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have demonstrated that global cerebral ischemia (GCI) causes neurological deficits and neuronal cell apoptosis. Calcitriol, a biologically active metabolite of vitamin D, exerts its endocrinological influence via nuclear vitamin D receptor. It is being assessed as an emerging therapeutic strategy in models of various medical conditions, including acute brain injury. The purpose of the present study was to investigate the neuroprotective effects of calcitriol on GCI and further refine the potential underlying mechanisms. A total of 145 male rats were assigned to 5 groups as follows: Sham group, GCI group, calcitriol treatment group, PD98059 treatment group and vehicle-treated group. Brain water content and neurologic severity score were assessed to evaluate the brain edema and neurological deficits of rats. Histopathological changes and ultrastructures of cells were observed via hematoxylin and eosin stain and transmission electron microscopy, respectively. Immunofluorescent staining and western blot analysis were used to assess the expression of proteins and their co-localization at the molecular level. The results demonstrated that post-GCI administration of calcitriol attenuated brain edema and improved neurological function in rats. Calcitriol also caused marked extracellular signal-regulated kinase 1/2 pathway activation, and thereby attenuated neuronal apoptosis. The present study provided novel clues for understanding the mechanisms by which calcitriol exerts its neuroprotective activity in a rat model of GCI.

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