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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2017

Open Access 01-12-2017 | Research article

In vivo evaluation of microglia activation by intracranial iron overload in central pain after spinal cord injury

Authors: Fan Xing Meng, Jing Ming Hou, Tian Sheng Sun

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2017

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Abstract

Background

Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent microglia activate in the remodeling of the brain after SCI.

Methods

An SCI-induced CP model was established in Sprague-Dawley rats that were randomly assigned to SCI, sham operation, deferoxamine (DFX), minocycline, and nitric oxide synthase inhibitor treatment groups. At 12 weeks, pain behavior and thermal pain threshold were evaluated in each group, and iron transferrin receptor (TfR)1 and ferritin (Fn) mRNA, as well as iron-regulatory protein (IRP)1, FN, lactoferrin, and nuclear factor (NF)-κB protein levels in the rat brains were measured. Microglia proliferation and differentiation and IRP1 expression were evaluated by immunohistochemistry.

Results

Autophagy was observed in rats after SCI, accompanied by reduced latency of thermal pain, increased iron content and IRP1 and NF-κB levels in the hindlimb sensory area, hippocampus, and thalamus, and decreased Fn levels in the hindlimb sensory area. TfR1 mRNA expression was upregulated in activated microglia. Treatment with an iron-chelating agent, or inhibitors of nitric oxide synthase or microglia suppressed microglia proliferation.

Conclusions

SCI may induce intracranial iron overload, which activates microglia via NF-κB signaling. Microglia secrete inflammatory factors that induce neuronal damage and lead to CP. Treatment with an iron-chelating agent or NF-κB or microglia inhibitors can relieve CP resulting from SCI.
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Metadata
Title
In vivo evaluation of microglia activation by intracranial iron overload in central pain after spinal cord injury
Authors
Fan Xing Meng
Jing Ming Hou
Tian Sheng Sun
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2017
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-017-0578-z

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