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腹腔注射依替唑仑可改善脊髓损伤小鼠的运动功能。

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

作者信息

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

机构信息

Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

出版信息

Neurotrauma Rep. 2023 Feb 22;4(1):82-96. doi: 10.1089/neur.2022.0071. eCollection 2023.

DOI:10.1089/neur.2022.0071
PMID:36874147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9983139/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/73dab94d8119/neur.2022.0071_figure7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/8fb619e89529/neur.2022.0071_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/d1011afb5e75/neur.2022.0071_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/c7a162cf060b/neur.2022.0071_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/437fbe52d4e1/neur.2022.0071_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/beaee2060f51/neur.2022.0071_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/5246c056a92d/neur.2022.0071_figure6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/73dab94d8119/neur.2022.0071_figure7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/8fb619e89529/neur.2022.0071_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/d1011afb5e75/neur.2022.0071_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/c7a162cf060b/neur.2022.0071_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/437fbe52d4e1/neur.2022.0071_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/beaee2060f51/neur.2022.0071_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/5246c056a92d/neur.2022.0071_figure6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/9983139/73dab94d8119/neur.2022.0071_figure7.jpg

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本文引用的文献

1
High-Dose Dependence and Cognitive Side Effects to Medical Prescription of Etizolam.依替唑仑医学处方的高剂量依赖性及认知副作用
Front Psychiatry. 2020 Nov 4;11:601827. doi: 10.3389/fpsyt.2020.601827. eCollection 2020.
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Sex-Related Differences in Anxiety and Functional Recovery after Spinal Cord Injury in Mice.小鼠脊髓损伤后焦虑和功能恢复的性别差异。
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Is etizolam a safe medication? Effects on psychomotor perfomance at therapeutic dosages of a newly abused psychoactive substance.
艾司唑仑是一种安全的药物吗?一种新出现的滥用精神活性物质治疗剂量对精神运动性能的影响。
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Homotaurine, a safe blood-brain barrier permeable GABA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis.牛磺酸是一种安全的血脑屏障可通透的 GABA-R 特定激动剂,可改善多发性硬化症小鼠模型的疾病状况。
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D-β-hydroxybutyrate promotes functional recovery and relieves pain hypersensitivity in mice with spinal cord injury.D-β-羟基丁酸可促进脊髓损伤小鼠的功能恢复并减轻疼痛超敏反应。
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The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation.抗炎化合物姜黄素通过免疫调节促进大鼠脊髓损伤后的运动和感觉恢复。
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Pain. 2016 Mar;157(3):687-697. doi: 10.1097/j.pain.0000000000000422.