E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model

Kikuchi, Kiyoshi; Setoyama, Kentaro; Takada, Seiya; Otsuka, Shotaro; Nakanishi, Kazuki; Norimatsu, Kosuke; Tani, Akira; Sakakima, Harutoshi; Kawahara, Ko-ichi; Hosokawa, Kazuya; Kiyama, Ryoji; Sumizono, Megumi; Tancharoen, Salunya; Maruyama, Ikuro; Hattori, Gohsuke; Morioka, Motohiro; Tanaka, Eiichiro; Uchikado, Hisaaki

doi:10.3390/ijms21113972

Open AccessArticle

E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model

by

Kiyoshi Kikuchi

^1,2,3,4,

Kentaro Setoyama

^5,†,

Seiya Takada

^3,†,

Shotaro Otsuka

³,

Kazuki Nakanishi

⁶,

Kosuke Norimatsu

⁶,

Akira Tani

⁶,

Harutoshi Sakakima

⁶,

Ko-ichi Kawahara

^3,7,

Kazuya Hosokawa

⁸,

Ryoji Kiyama

⁶

,

Megumi Sumizono

⁹

,

Salunya Tancharoen

⁴

,

Ikuro Maruyama

³,

Gohsuke Hattori

²,

Motohiro Morioka

²,

Eiichiro Tanaka

^1,* and

Hisaaki Uchikado

^2,10,*

¹

Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan

²

Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan

³

Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8520, Japan

⁴

Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand

⁵

Natural Science Center for Research and Education, Division of Laboratory Animal Science, Kagoshima University, Kagoshima 890-8520, Japan

⁶

Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8544, Japan

⁷

Laboratory of Functional Foods, Department of Biomedical Engineering, Osaka Institute of Technology, Osaka 535-8585, Japan

⁸

Research Institute, Fujimori Kogyo Co., Ltd., 1-10-1 Sachiura, Kanazawa-ku, Yokohama, Kanagawa 236-0003, Japan

⁹

Department of Rehabilitation, Faculty of Nursing and Welfare, Kyushu University of Nursing and Social Welfare, Tamana, Kumamoto 865-0062, Japan

¹⁰

Uchikado Neuro-Spine Clinic, Fukuoka 812-0893, Japan

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2020, 21(11), 3972; https://doi.org/10.3390/ijms21113972

Submission received: 2 April 2020 / Revised: 12 May 2020 / Accepted: 31 May 2020 / Published: 1 June 2020

(This article belongs to the Special Issue Neuroprotective Strategies 2020)

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Abstract

Perineural adhesions leading to neuropathy are one of the most undesirable consequences of peripheral nerve surgery. However, there are currently no widely used compounds with anti-adhesive effects in the field of peripheral nerve surgery. E8002 is a novel, anti-adhesive, multi-layer membrane that contains L-ascorbic acid (AA). Here, we investigated the effect and mechanism of E8002 in a rat sciatic nerve adhesion model. A total of 21 rats were used. Six weeks after surgery, macroscopic adhesion scores were significantly lower in the E8002 group (adhesion procedure followed by nerve wrapping with E8002) compared to the E8002 AA(−) group (adhesion procedure followed by nerve wrapping with the E8002 membrane excluding AA) and adhesion group (adhesion procedure but no treatment). Correspondingly, a microscopic examination revealed prominent scar tissue in the E8002 AA(−) and adhesion groups. Furthermore, an in vitro study using human blood samples showed that AA enhanced tissue-type, plasminogen activator-mediated fibrinolysis. Altogether, these results suggest that E8002 may exert an anti-adhesive action via AA and the regulation of fibrinolysis.

Keywords: peripheral nerve adhesion; anti-adhesive membrane; E8002; l-ascorbic acid; antioxidant

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MDPI and ACS Style

Kikuchi, K.; Setoyama, K.; Takada, S.; Otsuka, S.; Nakanishi, K.; Norimatsu, K.; Tani, A.; Sakakima, H.; Kawahara, K.-i.; Hosokawa, K.; et al. E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model. Int. J. Mol. Sci. 2020, 21, 3972. https://doi.org/10.3390/ijms21113972

AMA Style

Kikuchi K, Setoyama K, Takada S, Otsuka S, Nakanishi K, Norimatsu K, Tani A, Sakakima H, Kawahara K-i, Hosokawa K, et al. E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model. International Journal of Molecular Sciences. 2020; 21(11):3972. https://doi.org/10.3390/ijms21113972

Chicago/Turabian Style

Kikuchi, Kiyoshi, Kentaro Setoyama, Seiya Takada, Shotaro Otsuka, Kazuki Nakanishi, Kosuke Norimatsu, Akira Tani, Harutoshi Sakakima, Ko-ichi Kawahara, Kazuya Hosokawa, and et al. 2020. "E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model" International Journal of Molecular Sciences 21, no. 11: 3972. https://doi.org/10.3390/ijms21113972

APA Style

Kikuchi, K., Setoyama, K., Takada, S., Otsuka, S., Nakanishi, K., Norimatsu, K., Tani, A., Sakakima, H., Kawahara, K.-i., Hosokawa, K., Kiyama, R., Sumizono, M., Tancharoen, S., Maruyama, I., Hattori, G., Morioka, M., Tanaka, E., & Uchikado, H. (2020). E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model. International Journal of Molecular Sciences, 21(11), 3972. https://doi.org/10.3390/ijms21113972

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E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model

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