J Korean Orthop Assoc.  2008 Dec;43(6):783-790.

The Effect of Methylprednisolone and Riluzole on Axonal Growth after Acute Spinal Cord Injury in Rats

• Hong CH
• Yang JY
• Lee JK
• Song HS

Abstract

PURPOSE: To determine the effect of methylprednisolone (MP) and riluzole administration on axonal growth after spinal cord injury (SCI) in rats.
MATERIALS AND METHODS
Three Sprague Dawley rats (SD rat) served as controls (average 24 weeks of age) and 24 SCI SD rats scoring below 7 points on on Basso, Beattie, and Bresnahan open field test served as test subjects (total 27 SD rats; mean weight 581 g, range=427-613 g). Test subjects were divided into two groups of 12 subjects each. Group I was injected with saline (1 ml/kg) and group II was injected with MP (300 mg/kg) and riluzole (5 mg/kg) intraperitoneally. Four SD rats were sacrificed in each group at the following time points after SCI: days 1, 4, and 7. We completed behavioral testing, immunohistochemical staining and RT-PCR for chondroitin sulfate proteoglycans (CSPG), and microarrays for c-JUN, ATF-2, p53, and Elk-1.
RESULTS
On behavioral testing, group II showed superior results at only day 4 after SCI (p<0.05). On RT-PCR for CSPG, optical densities were 2.06 (ratio=Group I/Group II) and 2.11 at days 4 and 7, respectively. Microarray showed that lower expression of c-JUN in group II during the entire period (p< 0.05). ATF-2 showed lower expression in group II at days 4 and 7 (p<0.05). p53 showed lower expression in group I at day 1 (p<0.05). Elk-1 showed lower expression in group I at day 1 (p<0.05) and in group II at day 7 (p<0.05).
CONCLUSION
Simultaneous administration of MP and riluzole led to various changes in the MAPK pathway, and decreased CSPG. Therefore, this method has a protective effect on axonal regeneration after SCI in an SD rat model.

Keyword

Spinal cord injury; Methylprednisolone; Riluzole

MeSH Terms

Animals
Axons
Chondroitin Sulfate Proteoglycans
Methylprednisolone
Rats
Rats, Sprague-Dawley
Regeneration
Riluzole
Spinal Cord
Spinal Cord Injuries
Chondroitin Sulfate Proteoglycans
Methylprednisolone
Riluzole

Figure

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  Fig. 1 Open field score of the hind limbs after spinal cord injury in each groups. An open field score of 0 means no observable hind limb movement; an open field score 21 means normal hind limb movement.

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  Fig. 2 The immunohistochemical staining result; Noted differences of cavity size and the expression of CSPG (arrow); A (normal), B (group I) and C (group II) at 7th day.

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  Fig. 3 This picture shows the differences of the expression of CSPG by RT-PCR in each group; more expression of CSPG in group I at 4th and 7th day.

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  Fig. 4 The results of c-JUN, ATF-2, p53 and ELK-1 by microarray: The changes of c-JUN was on the increase immediately and then drop and increment in group I, but increased with the lapse of time in group II. The degree of c-JUN in group II at 7th day was less than in group I at 1st day. The expression of ATF-2 was increased with the lapse of time but group II was less expressed than group I with statistical differences. In p53, down-regulation with the lapse of time in group I. In group II, down-regulation was noted at 4th day. In ElK-1, up-regulation in group I and II at 4th day, and then plateau in group I, but down-regulation at 7th day in group II.

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