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镁增强了 NK1 拮抗剂给药对创伤性脑损伤后血脑屏障通透性和运动功能恢复的有益作用。

Magnesium enhances the beneficial effects of NK1 antagonist administration on blood-brain barrier permeability and motor outcome after traumatic brain injury.

机构信息

Discipline of Anatomy and Pathology, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.

Sansom Institute for Health Research, Division of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.

出版信息

Magnes Res. 2017 Aug 1;30(3):88-97. doi: 10.1684/mrh.2017.0427.

DOI:10.1684/mrh.2017.0427
PMID:29256408
Abstract

The current study investigated whether adding magnesium to an NK1 tachykinin receptor antagonist after traumatic brain injury would enhance efficacy to further reduce blood-brain barrier permeability and improve functional recovery compared to either treatment alone. Sprague-Dawley rats were injured using the impact acceleration model of diffuse brain injury, and received either no treatment, MgSO (30 mg/kg IV), the NK1 antagonist n-acetyl L tryptophan (2.5 mg/kg IP), or both agents combined. Animals were then killed at either 1, 5, or 24 h postinjury for determination of blood-brain barrier permeability using previously administered Evans blue dye or assessed for functional outcome over a 1-week period using the rotarod motor test. As expected, both MgSO and n-acetyl L tryptophan significantly reduced blood-brain barrier permeability and improved functional outcome. However, combined n-acetyl L tryptophan and MgSO was more effective at reducing blood-brain barrier permeability (P < 0.05) and improving functional outcome (P < 0.001) compared to the individual compounds. Our results demonstrate that combination therapy with magnesium and an NK1 antagonist may be a more effective therapy for TBI than either compound administered alone.

摘要

当前的研究旨在探究创伤性脑损伤后添加镁离子是否能增强 NK1 速激肽受体拮抗剂的疗效,从而进一步降低血脑屏障通透性并改善功能恢复,与单独使用任一药物相比。研究使用弥漫性脑损伤的撞击加速度模型对 Sprague-Dawley 大鼠进行损伤,然后分别给予无处理、MgSO(30 mg/kg IV)、NK1 拮抗剂 N-乙酰-L-色氨酸(2.5 mg/kg IP)或两者联合处理。动物在损伤后 1、5 或 24 小时处死,用之前给予的 Evans 蓝染料测定血脑屏障通透性,或在 1 周的时间内用转棒运动测试评估功能结果。正如预期的那样,MgSO 和 N-乙酰-L-色氨酸都能显著降低血脑屏障通透性并改善功能结果。然而,与单独使用这两种化合物相比,联合使用 N-乙酰-L-色氨酸和 MgSO 能更有效地降低血脑屏障通透性(P<0.05)和改善功能结果(P<0.001)。我们的结果表明,镁离子和 NK1 拮抗剂联合治疗可能是一种比单独使用任一化合物更有效的 TBI 治疗方法。

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