Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury

被引：11

作者：

Hanada, Mitsuru ^{[1
]}

Shinjo, Ryuichi ^{[2
]}

Miyagi, Michihito ^{[1
]}

Yasuda, Tatsuya ^{[1
]}

Tsutsumi, Koji ^{[3
]}

Sugiura, Yuki ^{[4
,5
]}

Imagama, Shiro ^{[2
]}

Ishiguro, Naoki ^{[2
]}

Matsuyama, Yukihiro ^{[1
]}

机构：

[1] Hamamatsu Univ Sch Med, Dept Orthopaed Surg, Hamamatsu, Shizuoka 4313192, Japan

[2] Nagoya Univ, Grad Sch Med, Dept Orthoped, Nagoya, Aichi 4668550, Japan

[3] Kitasato Univ, Sch Sci, Dept Biosci, Div Cell Biol,MInami Ku, Sagamihara, Kanagawa 2520373, Japan

[4] Keio Univ, Sch Med, Dept Biochem, Tokyo 1608582, Japan

[5] JST Precursory Res Embryon Sci Technol PRESTO Pro, Tokyo 1608582, Japan

来源：

JOURNAL OF THE NEUROLOGICAL SCIENCES | 2014年 / 337卷 / 1-2期

关键词：

Spinal cord injury; Arundic acid; S100; protein; Astrocyte; Secondary injury; Motor function; DELAYED INFARCT EXPANSION; PERMANENT FOCAL ISCHEMIA; ASTROCYTIC ACTIVATION; RECOVERY; LEVEL; ASTROGLIOSIS; INFLAMMATION; S-100-BETA; ANTAGONIST; PROTEIN;

D O I：

10.1016/j.jns.2013.12.008

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Arundic acid (ONO-2506) inhibits the production and release of S100 protein from astrocytes. While numerous studies have assessed the effect of ONO-2506 in the diseased brain, to the best of our knowledge, no study has examined the effect of ONO-2506 in spinal cord injury (SCI). In this study, we administered ONO-2506 to rats with SCI in order to evaluate its effectiveness in improving motor function and protecting against histological injury. Methods: All rats underwent laminectomy with SCI at the 10th thoracic vertebra. Rats were divided into 3 groups that received different concentrations of ONO-2506 as follows: 10 mg/kg (Group I) and 20 mg/kg (Group II). The third group (control group) was administered only saline. ONO-2506 or saline was administered by intravenous injection for a week after SCI. Recovery of motor function was assessed by determining the Basso, Beattie, and Bresnahan (BBB) scores and using the %grip test. Using immunohistochemistry, S100 protein and glial fibrillary acidic protein expression was assessed at week 12 post SO. Results: The BBB score of Group II was significantly better than that of the control group. At week 12 post SCI, the %grip was 43.0% in Group II and 20.3% in Group I. The score for the %grip test was greater for Group II than for the control group (7.0%); thus, motor function improvement appeared to be dose dependent. Regarding immuno-staining evaluation, S100 protein staining was lower in Group II compared to the control group, and the astrocytic morphology resembled that of normal spinal cord sections. The SCI lesion expanded from the injured site to both proximal and distal sites in the control group and in Group I. However, despite the presence of cavitation, secondary expansion of the SCI lesion was prevented in Group II as a result of inhibition of S100 protein. Conclusions: Administration of ONO-2506 (20 mg/kg) improves motor function and inhibits expansion of secondary injury, in SCI rats. (C) 2013 Elsevier B.V. All rights reserved.

引用

页码：186 / 192

页数：7

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