Vitamin D Receptor Activation Influences NADPH Oxidase (NOX2) Activity and Protects against Neurological Deficits and Apoptosis in a Rat Model of Traumatic Brain Injury.

Changmeng Cui,Junling Gao,Sixin Song,Yan Feng,Jianzhong Cui,Pei Jiang

doi:10.1155/2017/9245702

Abstract

Traumatic brain injury (TBI) is a worldwide phenomenon which results in significant neurological and cognitive deficits in humans. Vitamin D (VD) is implicated as a therapeutic strategy for various neurological diseases now. Recently, inhibition of the NADPH oxidase (NOX2) was reported to protect against oxidative stress (ROS) production. However, whether alterations in NOX2 expression and NOX activity are associated with calcitriol (active metabolite of VD) treatment following TBI remains unclear. In the present study, rats were randomly assigned to the sham, TBI, and calcitriol-treated groups. Calcitriol was administered intraperitoneally (2 μg/kg) at 30 min, 24 h, and 48 h after TBI insult. We observed that calcitriol treatment alleviated neurobehavioral deficits and brain edema following TBI. At the molecular levels, administration of calcitriol activated the expression of VDR and downregulated NOX2 as well as suppressed apoptosis cell rate in the hippocampus CA1 region of TBI rats. In conclusion, our findings indicate that the protective effects of calcitriol may be related to the modulation of NADPH oxidase and thereby ultimately inhibited the progression of apoptosis. Calcitriol may be promising as a protective intervention following TBI, and more study is warranted for its clinical testing in the future.

Highlights

Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in variation of immediate and delayed motor and cognitive deficiencies [1, 2]
We further examined whether the activation of vitamin D receptor (VDR) could attenuate neuron damage via modulation of the NADPH oxidase and cell apoptosis in the hippocampus CA1 region following TBI in rats
One rat was in the TBI model group, and the other was in the calcitriol group

Summary

Introduction

Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in variation of immediate and delayed motor and cognitive deficiencies [1, 2]. TBI is caused by both primary and secondary injury mechanisms. Primary damage is due to mechanical factors and occurs immediately at the moment of injury. It takes the form of intracranial hemorrhage, diffuse axonal injury (DAI), and surface contusions [4]. The secondary injury is delayed and is produced via complicating processes that are initiated at the moment of impact but do not present clinically for a period of hours to days following trauma. To find new effective therapeutic drugs or to develop novel therapeutic strategies is an important issue

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