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完整人免疫球蛋白球蛋白 -N 在点燃猫中的抗癫痫作用及其组织分布

Antiepileptic effects of globulin-N, an intact human immunoglobulin and its tissue-distribution in kindled cats.

作者信息

Hirayama H, Kurimoto T, Wada S, Machida N, Shikuma H, Shoji S, Horibe M

出版信息

Int J Clin Pharmacol Ther Toxicol. 1986 Mar;24(3):109-22.

PMID:3084394
Abstract

The antiepileptic effects of globulin-N, an intact human immunoglobulin was examined, using the amygdaloid kindled animals prepared by the method of Goddard et al. [1969] and Wada et al. [1974 b]. In the non-treated kindled cats, kindled convulsion and after-discharge (AD) were simultaneously created at 24-hour intervals by electrically stimulating generalized seizure-triggering threshold (GST) in amygdala, hippocampus and neocortex. The kindled cats, treated intravenously with 200 mg/kg of globulin-N, the generalized convulsion and AD produced by GST-stimulation disappeared entirely from 30 min to 8 days in 8 out of 10 cases. Furthermore, kindled cats treated with phenobarbital and phenytoin showed inhibition of GC and AD by GST-stimulation for 24-48 hours. Globulin-N was determined to have a plasma half-life of about 10 days in the kindled cats, and was presented immunohistochemically in the visceral organ, brain and spinal cord. The administered globulin-N passed through the BBB easily in the kindled cats with GST stimulation induced epileptic seizures, and was apparently taken up by the nerve and glial cells in the cerebral cortex and other deep structures of the central nervous system. These results may not only yield clues for the elucidation of the antiepileptic mechanisms of globulin-N, but may also support the clinical use of globulin-N in patients with intractable epilepsy [Ariizumi et al. 1982], including epileptic psychosis.

摘要

使用由戈达德等人[1969年]和和田等人[1974年b]的方法制备的杏仁核点燃动物,研究了完整的人免疫球蛋白球蛋白-N的抗癫痫作用。在未治疗的点燃猫中,通过电刺激杏仁核、海马体和新皮质中的全身性癫痫发作触发阈值(GST),每隔24小时同时引发点燃性惊厥和后放电(AD)。10只接受静脉注射200mg/kg球蛋白-N的点燃猫中,有8只在30分钟至8天内,由GST刺激产生的全身性惊厥和AD完全消失。此外,用苯巴比妥和苯妥英治疗的点燃猫,GST刺激引起的GC和AD受到抑制,持续24 - 48小时。在点燃猫中,球蛋白-N的血浆半衰期约为10天,免疫组织化学显示其存在于内脏器官、脑和脊髓中。在由GST刺激诱发癫痫发作的点燃猫中,给予的球蛋白-N很容易通过血脑屏障,并且明显被大脑皮质和中枢神经系统其他深部结构中的神经细胞和神经胶质细胞摄取。这些结果不仅可能为阐明球蛋白-N的抗癫痫机制提供线索,还可能支持球蛋白-N在包括癫痫性精神病在内的难治性癫痫患者中的临床应用[有泉等人,1982年]。

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