. 2018 May 18;19(5):1513.

doi: 10.3390/ijms19051513.

Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model

Kiyoshi Kikuchi^{1

2

3

4}, Kentaro Setoyama⁵, Takuto Terashi⁶, Megumi Sumizono⁷, Salunya Tancharoen⁸, Shotaro Otsuka⁹, Seiya Takada¹⁰, Kazuki Nakanishi¹¹, Koki Ueda¹², Harutoshi Sakakima¹³, Ko-Ichi Kawahara^{3

14}, Ikuro Maruyama¹⁵, Gohsuke Hattori¹⁶, Motohiro Morioka¹⁷, Eiichiro Tanaka¹⁸, Hisaaki Uchikado^{19

20}

Affiliations

¹ Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. koichi.kawahara@oit.ac.jp.
² Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. koichi.kawahara@oit.ac.jp.
³ Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. koichi.kawahara@oit.ac.jp.
⁴ Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand. koichi.kawahara@oit.ac.jp.
⁵ Division of Laboratory Animal Science, Natural Science Center for Research and Education, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. seto@m.kufm.kagoshima-u.ac.jp.
⁶ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k7200686@kadai.jp.
⁷ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k9380225@kadai.jp.
⁸ Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand. salunya.tan@mahidol.edu.
⁹ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k3360022@kadai.jp.
¹⁰ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k5082701@kadai.jp.
¹¹ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k9378361@kadai.jp.
¹² Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k1238698@kadai.jp.
¹³ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. sakaki@health.nop.kagoshima-u.ac.jp.
¹⁴ Laboratory of Functional Foods, Department of Biomedical Engineering Osaka Institute of Technology, 5-16-1 Omiya, Asahi-ku, Osaka 535-8585, Japan. koichi.kawahara@oit.ac.jp.
¹⁵ Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. maruyama@m2.kufm.kagoshima-u.ac.jp.
¹⁶ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. hattori_gohsuke@kurume-u.ac.jp.
¹⁷ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. mmorioka@med.kurume-u.ac.jp.
¹⁸ Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. eacht@med.kurume-u.ac.jp.
¹⁹ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. uchikado@me.com.
²⁰ Uchikado Neuro-Spine Clinic, 1-2-3 Naka, Hakata-ku, Fukuoka 812-0893, Japan. uchikado@me.com.

PMID: 29783695
PMCID: PMC5983581
DOI: 10.3390/ijms19051513

Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model

Kiyoshi Kikuchi et al. Int J Mol Sci. 2018.

. 2018 May 18;19(5):1513.

doi: 10.3390/ijms19051513.

Authors

Affiliations

¹ Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. koichi.kawahara@oit.ac.jp.
² Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. koichi.kawahara@oit.ac.jp.
³ Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. koichi.kawahara@oit.ac.jp.
⁴ Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand. koichi.kawahara@oit.ac.jp.
⁵ Division of Laboratory Animal Science, Natural Science Center for Research and Education, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. seto@m.kufm.kagoshima-u.ac.jp.
⁶ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k7200686@kadai.jp.
⁷ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k9380225@kadai.jp.
⁸ Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand. salunya.tan@mahidol.edu.
⁹ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k3360022@kadai.jp.
¹⁰ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k5082701@kadai.jp.
¹¹ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k9378361@kadai.jp.
¹² Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. k1238698@kadai.jp.
¹³ Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. sakaki@health.nop.kagoshima-u.ac.jp.
¹⁴ Laboratory of Functional Foods, Department of Biomedical Engineering Osaka Institute of Technology, 5-16-1 Omiya, Asahi-ku, Osaka 535-8585, Japan. koichi.kawahara@oit.ac.jp.
¹⁵ Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. maruyama@m2.kufm.kagoshima-u.ac.jp.
¹⁶ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. hattori_gohsuke@kurume-u.ac.jp.
¹⁷ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. mmorioka@med.kurume-u.ac.jp.
¹⁸ Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. eacht@med.kurume-u.ac.jp.
¹⁹ Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. uchikado@me.com.
²⁰ Uchikado Neuro-Spine Clinic, 1-2-3 Naka, Hakata-ku, Fukuoka 812-0893, Japan. uchikado@me.com.

PMID: 29783695
PMCID: PMC5983581
DOI: 10.3390/ijms19051513

Abstract

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin⁻eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.

Keywords: E8002; anti-adhesive membrane; failed back surgery syndrome; laminectomy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Effect of E8002 on neurological and macroscopic evaluations. (A) BBB score; (B) Macroscopic evaluation of skin; (C) Macroscopic evaluation of fascia; (D) Macroscopic evaluation of muscle. n.s., not significant.

**Figure 2**
Effect of E8002 on epidural scar tissues evaluated by HE staining. (A) Photomicrographs of epidural adhesions at the laminectomy sites. Arrows indicate scar tissue. The square indicates vacuolation above the dura mater; (B) Representative images of HE staining for fibroblasts and inflammatory cells in the control group and E8002 group (original magnification, ×200). Scale bars, 100 μm; (C) Representative images of HE staining for fibroblasts in the control group and E8002 group (original magnification, ×400). Scale bars, 100 μm; (D) Counts of fibroblast density; (E) Representative images of HE staining for inflammatory cells in the control group and E8002 group (original magnification, ×400). Scale bars, 100 μm; (F) Cell counts of inflammatory cells.

**Figure 3**
Effect of E8002 on epidural scar tissues evaluated by aldehyde fuchsin-Masson Goldner staining. Representative images of aldehyde fuchsin-Masson Goldner staining in the control group and E8002 group are shown (original magnification: upper panels ×200, lower panels ×400) (scale bars: **upper panels** 100 μm, **lower panels** 50 μm).

See this image and copyright information in PMC

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Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model

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Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model

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Conflict of interest statement

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