Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury

H Arima; M Hanada; T Hayasaka; N Masaki; T Omura; D Xu; T Hasegawa; D Togawa; Y Yamato; S Kobayashi; T Yasuda; Y Matsuyama; M Setou

doi:10.1016/j.neuroscience.2014.03.012

Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury

Neuroscience. 2014 Jun 6:269:1-10. doi: 10.1016/j.neuroscience.2014.03.012. Epub 2014 Mar 20.

Authors

H Arima¹, M Hanada¹, T Hayasaka², N Masaki², T Omura¹, D Xu¹, T Hasegawa¹, D Togawa¹, Y Yamato¹, S Kobayashi¹, T Yasuda¹, Y Matsuyama¹, M Setou³

Affiliations

¹ Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
² Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
³ Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: setou@hama-med.ac.jp.

PMID: 24657456
DOI: 10.1016/j.neuroscience.2014.03.012

Abstract

The interleukin (IL)-6 pathway plays an important role in recovery after spinal cord injury (SCI). The anti-IL-6 receptor antibody MR16-1 has been shown to suppress inflammation after SCI and promote recovery of motor function. The purpose of this study was to analyze the effects of MR16-1 on the expression patterns of phospholipids in the spinal cord in a mouse model of SCI. Eight-week-old C57BL/6JJmsSlc mice were used in this study. Laminectomy was performed at the ninth and tenth thoracic levels (T9-T10), and contusion injury of the spinal cord was induced at level T10. Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (MR16-1 group) or a single dose of phosphate-buffered saline of the same volume (control group). Imaging mass spectrometry was performed to visualize phosphatidylcholine (PC) expression in the spinal cord 7 days after SCI. We found that MR16-1 treatment suppressed the infiltration of immune cells after SCI, and was able to increase the locomotor function post-injury. Phospholipid imaging revealed that the MR16-1 was able to prevent the reduction of docosahexaenoic acid (DHA)-containing PC in comparison with the control group. We also observed high levels of glial fibrillary acidic protein (GFAP) at the site of DHA-containing PC expression in the MR16-1 group. These results suggest that MR16-1 treatment influences the DHA-containing PC composition of GFAP-positive cells at the injury site as early as 7 days post-SCI.

Keywords: IL-6; docosahexaenoic acid; imaging mass spectrometry; phosphatidylcholine; phospholipids; spinal cord injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / pharmacology*
Disease Models, Animal
Docosahexaenoic Acids / metabolism*
Female
Glial Fibrillary Acidic Protein
Hindlimb / drug effects
Hindlimb / physiopathology
Interleukin-6 / metabolism*
Locomotion / drug effects
Locomotion / physiology
Macrophages / drug effects
Macrophages / physiology
Mice, Inbred C57BL
Microglia / drug effects
Microglia / physiology
Nerve Tissue Proteins / metabolism
Neuroprotective Agents / pharmacology*
Phosphatidylcholines / metabolism*
Random Allocation
Recovery of Function / drug effects
Recovery of Function / physiology
Signal Transduction / drug effects
Spinal Cord / drug effects
Spinal Cord / pathology
Spinal Cord / physiopathology
Spinal Cord Injuries / drug therapy*
Spinal Cord Injuries / pathology
Spinal Cord Injuries / physiopathology*
Thoracic Vertebrae

Substances

Antibodies, Monoclonal
Glial Fibrillary Acidic Protein
Interleukin-6
Nerve Tissue Proteins
Neuroprotective Agents
Phosphatidylcholines
glial fibrillary astrocytic protein, mouse
interleukin-6, mouse
Docosahexaenoic Acids