J Korean Orthop Assoc. 2007 Feb;42(1):106-114. Korean.
Published online Feb 28, 2007.
Copyright © 2007 The Korean Orthopaedic Association
Original Article

Agonist for the Control of Apotosis through the Study of Cytokine Expression after Spinal Cord Injury in Rats

Jun Young Yang, M.D., and K. Daniel Riew, M.D.*
    • Department of Orthopaedic Surgery, School of Medicine, Chungnam National University, Research Institute of Medical Sciences, Daejeon, Korea.
    • *Barnes-Jewish Hospital, Washington University, USA.

Abstract

Purpose

To analyze the cytokines that appear after a spinal cord injury in rats and to determine the agonists that regulate apoptosis.

Materials and Methods

Sixty female Sprague-Dawley rats were anesthetized, and a laminectomy was performed at the 9th thoracic vertebra. The spinal cord injury was induced by dropping a 10 gm weight at a height of 20 mm. The subjects were divided into 5 groups. Group I was administered aminoguanidine, group II was administered GM-CSF, group III was administered riluzole, group IV was administered erythropoietin, and group V was administered methylprednisolone. A control group was administered normal saline. The results were assessed using the Tarlov motor grading method. In 1, 3, 5 and 7 days after the spinal cord injury, the rats were sacrificed and evaluated using the syringomyelic cavity size. Immunohistochemical staining for e-NOS and RT-PCR for XIAP were also performed.

Results

Groups I, III, and V showed significantly different results in terms of the motor recovery and inhibition of increase in the syringomyelic cavity compared with the other groups (p<0.05). The e-NOS activity was observed in groups I, III, and V. The other groups showed almost no e-NOS activity. On the RT-PCR, groups I, III, and V showed significantly different results in terms of XIAP expression with time compared with the other groups.

Conclusion

Steroids, NOS inhibitors and sodium channel inhibitors appear to be important factors for regulating apoptosis in the early stage of a spinal cord injury. Further study will be needed to develop new pharmaceuticals with synergic effects on spinal cord injuries.

Keywords
Apoptosis; Spinal cord injury

Figures

Fig. 1
A is longest cavity length and B is transverse cord length over the longest cavity length.

Fig. 2
Methylprednisolon, aminoguanidine, and sodium channel blocker show similar effects but there are significant differences between groups I, III, and V and the Control, II and IV groups.

Fig. 3
(A) control in H-E stain, (B) group V in H-E stain. The cavity size of the control group is three times than group V, methylprednisolon administraton group.

Fig. 4
The largest cavities was noted in the control, II and IV. There are significant differences between the control, II and IV, and groups I, III, and V. These results are similar to the result of the recovery of motor function.

Fig. 5
(A) Noted expression eNOS activity (B) groups I, V and III noted expression eNOS activity.

Fig. 6
The groups administered aminoganidine as a NO inhibitor, riluzole as a sodium channel blocker and methylprednisolone show prominent XIAP expression according with time.

Tables

Table 1
Experimental Group

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