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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
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使用超声波增强oxime在大脑中的有效性,以抵消神经毒剂暴露
Lépinard Lucie1, Leterrier Sarah2, Jourdain Laurène2
1IRBA, Département Toxicologie et Risques Chimiques, Brétigny-sur-Orge, France; Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay, France.
概括
使用微气泡的聚焦超声波 (FUS) 增强了对大脑的氧化物输送,改善了乙胆化酶 (AChE) 反激活和器官酸盐 (OP) 暴露后的生存.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 生物医学工程 生物医学工程
背景情况:
- 器官酸盐 (OPs) 抑制乙胆酶 (AChE),导致神经毒性和认知障碍,这是由于抗药物在血脑屏障 (BBB) 透程度有限.
- 带有微气泡的跨聚焦超声波 (FUS) 可以暂时破坏BBB,以加强向中枢神经系统 (CNS) 的药物输送.
研究的目的:
- 评估FUS介导的氧化物 (2-PAM,HI-6) 在OP暴露后大脑中ACHE重新激活的疗效.
- 评估FUS增强氧化物治疗对VX暴露的小鼠模型中神经恢复和生存的影响.
主要方法:
- 暴露于VX次致命和超致命剂量的小鼠接受HI-6或2-PAM治疗,有或没有FUS介导的BBB中断.
- 测量了海马中的ACHE活性,以及短期恢复,24小时生存率和促炎细胞因子 (IL-6,MIP-1α) 的表达.
主要成果:
- 与单独使用HI-6相比,HI-6 + FUS显著增加了海马中的ACHE活性.
- 2-PAM + FUS对 AChE 反激活没有显著改善.
- HI-6 + FUS治疗导致短期恢复,24小时生存率增加和VX暴露后神经炎症 (IL-6,MIP-1α) 减少.
结论:
- 由FUS介导的BBB中断是一种有前途的策略,可以增强氧化物向大脑的输送,从而提高OP中毒的治疗疗效.
- 与FUS结合的HI-6显示出减轻中枢神经系统损伤的潜力,并改善有机暴露的结果.
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