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

Mitsuru Hanada, Ryuichi Shinjo, Michihito Miyagi, Tatsuya Yasuda, Koji Tsutsumi, Yuki Sugiura, Shiro Imagama, Naoki Ishiguro, Yukihiro Matsuyama

Research output: Contribution to journalArticle

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Abstract

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 SCI. 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 immunostaining 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.

Original languageEnglish
Pages (from-to)186-192
Number of pages7
JournalJournal of the Neurological Sciences
Volume337
Issue number1-2
DOIs
Publication statusPublished - 2014 Feb 15

Fingerprint

Spinal Cord Injuries
Wounds and Injuries
S100 Proteins
Hand Strength
Control Groups
Thoracic Vertebrae
ONO2506
Laminectomy
Glial Fibrillary Acidic Protein
Recovery of Function
Brain Diseases
Intravenous Injections
Astrocytes
Spinal Cord
Immunohistochemistry
Staining and Labeling

Keywords

  • Arundic acid
  • Astrocyte
  • Motor function
  • S100 protein
  • Secondary injury
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury. / Hanada, Mitsuru; Shinjo, Ryuichi; Miyagi, Michihito; Yasuda, Tatsuya; Tsutsumi, Koji; Sugiura, Yuki; Imagama, Shiro; Ishiguro, Naoki; Matsuyama, Yukihiro.

In: Journal of the Neurological Sciences, Vol. 337, No. 1-2, 15.02.2014, p. 186-192.

Research output: Contribution to journalArticle

Hanada, M, Shinjo, R, Miyagi, M, Yasuda, T, Tsutsumi, K, Sugiura, Y, Imagama, S, Ishiguro, N & Matsuyama, Y 2014, 'Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury', Journal of the Neurological Sciences, vol. 337, no. 1-2, pp. 186-192. https://doi.org/10.1016/j.jns.2013.12.008
Hanada, Mitsuru ; Shinjo, Ryuichi ; Miyagi, Michihito ; Yasuda, Tatsuya ; Tsutsumi, Koji ; Sugiura, Yuki ; Imagama, Shiro ; Ishiguro, Naoki ; Matsuyama, Yukihiro. / Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury. In: Journal of the Neurological Sciences. 2014 ; Vol. 337, No. 1-2. pp. 186-192.
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abstract = "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 SCI. 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 immunostaining 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.",
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author = "Mitsuru Hanada and Ryuichi Shinjo and Michihito Miyagi and Tatsuya Yasuda and Koji Tsutsumi and Yuki Sugiura and Shiro Imagama and Naoki Ishiguro and Yukihiro Matsuyama",
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T1 - Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury

AU - Hanada, Mitsuru

AU - Shinjo, Ryuichi

AU - Miyagi, Michihito

AU - Yasuda, Tatsuya

AU - Tsutsumi, Koji

AU - Sugiura, Yuki

AU - Imagama, Shiro

AU - Ishiguro, Naoki

AU - Matsuyama, Yukihiro

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N2 - 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 SCI. 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 immunostaining 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.

AB - 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 SCI. 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 immunostaining 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.

KW - Arundic acid

KW - Astrocyte

KW - Motor function

KW - S100 protein

KW - Secondary injury

KW - Spinal cord injury

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