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首页> 外文期刊>Life sciences >Partial hepatectomy aggravates cyclosporin A-induced neurotoxicity by lowering the function of the blood-brain barrier in mice.
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Partial hepatectomy aggravates cyclosporin A-induced neurotoxicity by lowering the function of the blood-brain barrier in mice.

机译：肝部分切除术通过降低小鼠血脑屏障的功能来加重环孢菌素A诱导的神经毒性。

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AIMS: Cyclosporin A, a calcineurin inhibitor, produces neurotoxicity with relatively high frequency in organ-transplanted patients. The aim of the present study was to clarify whether acute liver failure (ALF) simulated to the transient liver dysfunction at an early phase after liver transplantation increases the susceptibility to cyclosporin A-induced neurotoxicity through the blood-brain barrier (BBB) dysfunction. MAIN METHODS: The right internal, left lateral and left internal lobes in male ddy mice were surgically excised under sodium pentobarbital anesthesia. Effect of cyclosporin A on harmine-induced tremors was examined and BBB permeability to (3)[H]cyclosporin A was assessed in partially (70%) hepatectomized mice at postoperative days 1, 3 and 7. KEY FINDINGS: Patrial hepatectomy aggravated harmine-induced tremors. Cyclosporin A (50mg/kg, i.p.) markedly augmented harmine-induced tremors in partially hepatectomized mice at postoperative day 1. Consistent with these behavioral findings, the brain uptake of (3)[H]cyclosporin A in mice injected with (3)[H]cyclosporin A into the jugular vein at postoperative day 1 was significantly increased by partial hepatectomy compared with sham operation. SIGNIFICANCE: Our results indicate that ALF increases BBB permeability to cyclosporin A by lowering the function of P-glycoprotein and tight junctions, consequently leading to augmentation of cyclosporin A-induced neurotoxicity. The possibility that cyclosporin A increases the risk of neurotoxicity including tremors at an early phase of liver transplantation must be considered.
机译：目的：环孢菌素A，一种钙调神经磷酸酶抑制剂，在器官移植患者中以相对较高的频率产生神经毒性。本研究的目的是阐明在肝移植后早期模拟为短暂性肝功能障碍的急性肝衰竭（ALF）是否通过血脑屏障（BBB）功能障碍增加了对环孢菌素A诱导的神经毒性的敏感性。主要方法：在戊巴比妥钠麻醉下通过手术切除雄性Ddy小鼠的右内，左外侧和左内叶。在术后第1、3和7天，检查了部分（70％）肝切除的小鼠中环孢菌素A对由海因引起的震颤的作用，并评估了BBB对（3）[H]环孢菌素A的通透性。诱发的震颤。在术后第1天，部分肝切除的小鼠中环孢菌素A（50mg / kg，ip）明显增强了由甜菜碱引起的震颤。与这些行为研究结果一致，注射了（3）[]的小鼠大脑吸收了（3）[H]环孢菌素A。与假手术相比，部分肝切除术后第1天H]环孢菌素A进入颈静脉的比例明显增加。意义：我们的结果表明，ALF通过降低P-糖蛋白和紧密连接的功能来增加BBB对环孢菌素A的通透性，从而导致环孢菌素A诱导的神经毒性增强。必须考虑在肝移植的早期，环孢菌素A增加神经毒性（包括震颤）风险的可能性。

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