Saruta Kenya, Fukutoku Tatsuhiro, Kumagai Gentaro, Nagaoki Toshihide, Tsukuda Manami, Nitobe Yohshiro, Wada Kanichiro, Asari Toru, Fujita Taku, Sasaki Isamu, Nikaido Yoshikazu, Shimoyama Shuji, Ueno Shinya, Ishibashi Yasuyuki
Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Neurotrauma Rep. 2023 Feb 22;4(1):82-96. doi: 10.1089/neur.2022.0071. eCollection 2023.
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.
神经炎症发生在脊髓损伤(SCI)的急性期,并抑制神经再生。在小鼠模型中,艾司唑仑(ETZ)是一种强效抗焦虑药,对SCI的影响尚不清楚。本研究调查了短期给予ETZ对SCI后小鼠神经炎症和行为的影响。从SCI后的第二天开始,我们每天腹腔注射ETZ(0.5mg/kg),持续7天。小鼠被随机分为三组(假手术组:仅行椎板切除术;生理盐水组;ETZ组)。在SCI后第7天,使用酶联免疫吸附测定法测量损伤脊髓中心的炎性细胞因子浓度,以评估急性期的脊髓炎症。在手术前一天以及手术后第7、14、28和42天进行行为分析。行为分析包括使用旷场试验评估焦虑样行为、使用Basso小鼠量表评估运动功能以及使用机械和热测试评估感觉功能。脊髓手术后急性期,ETZ组的炎性细胞因子浓度显著低于生理盐水组。SCI后,ETZ组和生理盐水组之间的焦虑样行为和感觉功能相当。给予ETZ可减轻脊髓神经炎症并改善运动功能。γ-氨基丁酸A型受体激动剂可能是SCI患者有效的治疗药物。