MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.

Dingding Li,Donghe Han,Xifan Mei,Zhanghui Wan,Zhiyuan Liu,Guannan Wang,Kai Gao,Hongyu Wang,Tianchen Yao,Wei Gao,Chenyuan Li,Haihong Li,Jing Bi

doi:10.1155/2016/6090316

Abstract

Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI.

Highlights

Spinal cord injury (SCI) has been studied for over 100 years, and its harm that lies in causing lifelong disability and psychological burden have been described in considerable papers [1]
Microglia activation is a feature of secondary mechanisms of SCI; some of the properties of that are beneficial, for example, protecting spinal cord from infections and confining injury regions [33, 34]
In our in vitro studies, we report that cell viability of microglia was significantly reduced by MP administration when microglia were undergoing activation (Figure 5(a))

Summary

Introduction

Spinal cord injury (SCI) has been studied for over 100 years, and its harm that lies in causing lifelong disability and psychological burden have been described in considerable papers [1]. Secondary injury mechanisms, which are more pivotal in the recovery of SCI, include inflammation, oxidization, immunological reaction, electrolyte disorder, vascular damage, and loss of energy balance [4]. MP has protective effect on vascular injury after SCI, through diverse aspects of tissue edema, vascular permeability, and polymorphonuclear cell infiltration [8]. Previous studies have reported that autophagic cell death occurs in various diseases. Autophagic cell death was induced through glutamate-mediated GSK-3β activation in astrocytes [12] or through elevation of Beclin-1 in neurons [13] after traumatic brain injury. We demonstrated that spinal cord zinc changes after SCI. We suppose that the neuronal protective role of MP may relate to the activation of autophagy through the changes of zinc, as an ionic messenger

Methods and Materials

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