title: Arundic acid (ONO-2506) inhibits secondary injury and improves motor function in rats with spinal cord injury.
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.
authors.affiliation: Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: mitsuruhanada@gmail.com.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hanada
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shinjo
authors.affiliation: Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Michihito
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, MInami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsutsumi
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan; JST Precursory Research for Embryonic Science Technology (PRESTO) Project, Tokyo 160-8582, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Imagama
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: spine-yu@hama-med.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D002210:Caprylates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology; D053580:Muscle Strength / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000401:mortality; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D002210:Caprylates; D009419:Nerve Tissue Proteins; C459360:ONO2506; C488416:Tubb3 protein, rat; D014404:Tubulin
keywords: Arundic acid; Astrocyte; Motor function; S100 protein; Secondary injury; Spinal cord injury