Original Article

Spinal Cord (2008) 46, 425–431; doi:10.1038/sj.sc.3102163; published online 4 March 2008

Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury

T Morino1, T Ogata1, J Takeba1 and H Yamamoto1

1Department of Orthopaedic Surgery, Ehime University, School of Medicine, Tohon, Ehime, Japan

Correspondence: Dr T Morino, Department of Orthopaedic Surgery, Ehime University, School of Medicine, Shizukawa, Tohon, Ehime 791-0295, Japan. E-mail: morino@m.ehime-u.ac.jp

Received 6 July 2007; Revised 18 October 2007; Accepted 22 November 2007; Published online 4 March 2008.

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Abstract

Study Design:

 

A basic study using a spinal cord injury (SCI) model in rats.

Objectives:

 

The effect of mild hypothermic treatment on histological changes and motor function after a rat spinal cord compression injury was assessed.

Methods:

 

Mild spinal cord compression was performed at the eleventh thoracic vertebral level by a 20 g weight for 20 min. Rats in the mild hypothermic model were kept at a body temperature of 33 °C and rats in the normothermic group were kept at 37 °C for 1 h from beginning of compression. Motor function was evaluated by measuring the frequency of standing. Microglia were stained by isolectin B4 and observed in the compressed portion of the spinal cord. The amount of tumor necrosis factor-alpha (TNF-alpha) in the compressed spinal cord was measured by the ELISA method.

Results:

 

In the normothermic rats, microglia proliferated up to 72 h after the compression. Proliferation was substantially inhibited at 48 and 72 h after compression in the hypothermic rats. The motor function of the hypothermic rats improved at 48 and 72 h after the compression, whereas no improvement was seen in the normothermic rats. The amount of TNF-alpha in the compressed portion of the spinal cord was lower in hypothermic rats compared with normothermic rats throughout the experiment.

Conclusions:

 

These results suggest that hypothermic treatment is effective for the amelioration of delayed motor dysfunction via inhibition of microglial inflammatory responses.

Keywords:

hypothermia, spinal cord injury, microglia, tumor necrosis factor-alpha

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