International Journal of Molecular Sciences (Jun 2020)

E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of <span style="font-variant: small-caps">l</span>-Ascorbic Acid in a Rat Sciatic Nerve Model

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

DOI
https://doi.org/10.3390/ijms21113972
Journal volume & issue
Vol. 21, no. 11
p. 3972

Abstract

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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.

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