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

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.

• Authors: Fan Xing Meng, Jing Ming Hou, Tian Sheng Sun
• Journal: Journal of orthopaedic surgery and research (J Orthop Surg Res) Vol. 12 Issue 1 Pg. 75 (May 18 2017) ISSN: 1749-799X [Electronic] England
• PMID: 28521818 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Receptors, Transferrin
• Tfrc protein, rat

Topics

• Animals
• Cerebral Cortex (metabolism, pathology)
• Female
• Iron Overload (complications, metabolism, pathology)
• Microglia (metabolism, pathology)
• Pain (etiology, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Transferrin (biosynthesis)
• Spinal Cord Injuries (complications, metabolism, pathology)
• Thoracic Vertebrae