脑室给药糖madex对大鼠中枢神经系统的影响

H. A. Erdost, Elvan Oçmen, S. Duru, Burc Aydın, A. N. Gokmen
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引用次数: 1

摘要

简介:Sugammadex (Bridon®)(SUG)是最近开发的神经肌肉阻滞逆转剂。与其他现有药物不同,SUG还能在短时间内逆转深层神经肌肉阻塞。在正常患者中,SUG通过血脑屏障(BBB)的比例非常低。然而,在血脑屏障完整性降低的患者中,SUG通过血脑屏障的比例更高。由于SUG在正常患者中通过血脑屏障的比例很低,因此只有少量的研究探讨了SUG对中枢神经系统(CNS)的影响。在本研究中,我们旨在评估脑室内直接给药SUG对大鼠中枢神经系统的影响。材料与方法:选取体重250 ~ 280 g、运动活动正常的Wistar-Albino大鼠36只。麻醉采用50 mg/kg硫喷妥钠腹腔注射。将大鼠随机分为6组,其中1组为对照组。试验组小鼠分别经脑室内插管给予糖madex 2、4、8、16、32 mg/kg。根据5分制评估SUG对中枢神经系统的影响。结果:任何剂量(2、4、8、16和32 mg/kg)脑室内SUG给药均未导致行为状态、运动活动或姿势的任何改变。给药后无强直性阵挛性惊厥或癫痫发作。讨论:在正常患者中,SUG几乎不能通过血脑屏障。然而,在某些患者中,这种药物通过血脑屏障的比例更高。因此,研究SUG对中枢神经系统的影响是一个新兴的实验课题。在我们的研究中,我们没有发现SUG对中枢神经系统的任何不良影响,即使是在高剂量的脑室内直接给药。然而,有一项研究表明,在有SUG存在的细胞培养中,凋亡细胞死亡增加,因此很难断言SUG对中枢神经系统没有任何不良影响。上述研究的作者指出,胆固醇水平的降低与细胞凋亡之间存在联系。可以推测,活体动物中的某些机制可能会恢复在SUG存在下发生的胆固醇水平下降,从而防止细胞凋亡。结论:在本研究中,SUG未对大鼠中枢神经系统造成任何不良影响。进一步的研究评估SUG与神经元胆固醇控制机制之间的关系是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of Intracerebroventricular Sugammadex Administration on Central Nervous System in Rats
Introduction: Sugammadex (Bridon ®) (SUG) is a recently developed neuromuscular block reversing agent. SUG can reverse also deep neuromuscular blockages in a short time period unlike other existing agents. SUG passes across blood brain barrier (BBB) in a very low ratio in normal patients. However SUG may pass the BBB in a higher ratio in patients whom BBB integrity is decreased. Since SUG passes BBB in a low ratio in normal patients there are only a small amount of studies investigating effects of this agent on central nervous system (CNS). In this study we aimed to assess the effects of SUG administered directly to intracerebroventricular space on CNS system of rats. Materials and Method: A total of 36 Wistar-Albino rats with normal motor activity weighting between 250-280 g were included in this study. Anesthesia was achieved with intraperitoneal 50 mg/kg sodium thiopental. The rats were divided into 6 equal groups randomly as one group being the control group. The experiment groups were received 2,4,8,16 and 32 mg/kg sugammadex via intracerebroventricular cannula. Effects of the SUG on CNS were assessed based on a 5 point scale. Results: Intracerebroventricular SUG administration did not result in any changes in behavioral status, locomotor activity or posture at any doses (2,4,8,16 and 32 mg/kg). There was no tonic clonic convulsion or seizure development following the sugammadex administration. Discussion: SUG barely passes the BBB in normal patients. However it was stated that this drug can pass BBB in higher ratios in certain patients. Therefore investigating the effects of SUG on CNS is an emerging subject of experiments. In our study we could not find any adverse effect of SUG on CNS even at high doses administered directly to intracerebroventricular space. However presence of a study indicating an increase in apoptotic cell death in cell cultures in presence of SUG makes it difficult to make a statement that SUG does not have any adverse effect on CNS. The authors of the aforementioned study stated a connection between decrease in cholesterol levels and apoptosis. It can be speculated that some mechanisms in live animals may restore this decrease in cholesterol levels occurring in presence of SUG therefore prevents the cells from apoptosis. Conclusion: In our study SUG did not cause any adverse effect on CNS in rats. Further studies assessing the relationship between SUG and cholesterol control mechanisms in neurons are necessary in order to make a certain statement.
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