Neurotrauma Reports (Feb 2023)

Intraperitoneal Administration of Etizolam Improves Locomotor Function in Mice After Spinal Cord Injury

  • Kenya Saruta,
  • Tatsuhiro Fukutoku,
  • Gentaro Kumagai,
  • Toshihide Nagaoki,
  • Manami Tsukuda,
  • Yohshiro Nitobe,
  • Kanichiro Wada,
  • Toru Asari,
  • Taku Fujita,
  • Isamu Sasaki,
  • Yoshikazu Nikaido,
  • Shuji Shimoyama,
  • Shinya Ueno,
  • Yasuyuki Ishibashi

DOI
https://doi.org/10.1089/NEUR.2022.0071
Journal volume & issue
Vol. 4, no. 1
pp. 82 – 96

Abstract

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Neuroinflammation occurs in the acute phase of spinal cord injury (SCI) and inhibits neural regeneration. In mouse models, etizolam (ETZ) is a strong anxiolytic with unclear effects on SCI. This study investigated the effects of short-term administration of ETZ on neuroinflammation and behavior in mice after SCI. We administrated an ETZ (0.5?mg/kg) daily intraperitoneal injection from the day after SCI for 7 days. Mice were randomly divided into three groups (sham group: only laminectomy, saline group, and ETZ group). Inflammatory cytokine concentrations in the injured spinal cord epicenter were measured using an enzyme-linked immunosorbent assay on day 7 after SCI to evaluate spinal cord inflammation in the acute phase. Behavior analysis was performed the day before surgery and on days 7, 14, 28, and 42 after surgery. The behavioral analysis included anxiety-like behavior using the open field test, locomotor function using the Basso Mouse Scale, and sensory function using the mechanical and heat test. Inflammatory cytokine concentrations were significantly lower in the ETZ group than in the saline group in the acute phase after spinal surgery. After SCI, anxiety-like behaviors and sensory functions were comparable between the ETZ and saline groups. ETZ administration reduced neuroinflammation in the spinal cord and improved locomotor function. Gamma-amino butyric acid type A receptor stimulants may be effective therapeutic agents for patients with SCI.

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