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新型合成核苷类似物COA-Cl在脑出血急性期发挥神经保护作用。

COA-Cl, a Novel Synthesized Nucleoside Analog, Exerts Neuroprotective Effects in the Acute Phase of Intracerebral Hemorrhage.

作者信息

Lu Feng, Nakamura Takehiro, Okabe Naohiko, Himi Naoyuki, Nakamura-Maruyama Emi, Shiromoto Takashi, Narita Kazuhiko, Tsukamoto Ikuko, Xi Guohua, Keep Richard F, Miyamoto Osamu

机构信息

Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.

Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa, Japan.

出版信息

J Stroke Cerebrovasc Dis. 2016 Nov;25(11):2637-2643. doi: 10.1016/j.jstrokecerebrovasdis.2016.07.006. Epub 2016 Aug 2.

Abstract

BACKGROUND

A previous study in our laboratory showed the neuroprotective effects of COA-Cl, a novel synthesized adenosine analog, in a rat cerebral ischemia model. The purpose of the present study was to evaluate the neuroprotective effects of COA-Cl in intracerebral hemorrhage (ICH), another common type of stroke, and investigate potential mechanisms of action.

METHODS

Adult Sprague-Dawley rats received an injection of 100 µl autologous whole blood into the right basal ganglia. COA-Cl (30 µg/kg) was injected intracerebroventricularly 10 minutes after ICH. A battery of motor deficit tests were performed at 1 day, 3 days, 5 days, and 7 days after ICH. To investigate the mechanism of action, brain water content, TUNEL staining and 8-OHdG immunostaining, and ELISA (to assess oxidative stress) were used.

RESULTS

COA-Cl treatment significantly attenuated sensorimotor deficits and reduced brain edema 1 day after ICH. Furthermore, the numbers of perihematomal TUNEL- and 8-OHdG-positive cells were significantly decreased in COA-Cl treated ICH rats.

CONCLUSIONS

These results indicate that COA-Cl has neuroprotective effects in ICH. Furthermore, our study provides evidence that COA-Cl may reduce oxidative stress, which may be one mechanism underlying its neuroprotective effects.

摘要

背景

我们实验室之前的一项研究表明,新型合成腺苷类似物COA-Cl在大鼠脑缺血模型中具有神经保护作用。本研究的目的是评估COA-Cl在另一种常见中风类型——脑出血(ICH)中的神经保护作用,并探讨其潜在的作用机制。

方法

成年Sprague-Dawley大鼠右侧基底节注射100 μl自体全血。ICH后10分钟经脑室注射COA-Cl(30 μg/kg)。在ICH后1天、3天、5天和7天进行一系列运动功能缺损测试。为研究作用机制,采用了脑含水量测定、TUNEL染色和8-OHdG免疫染色以及ELISA(用于评估氧化应激)。

结果

COA-Cl治疗显著减轻了ICH后1天的感觉运动功能缺损并减轻了脑水肿。此外,在接受COA-Cl治疗的ICH大鼠中,血肿周围TUNEL和8-OHdG阳性细胞数量显著减少。

结论

这些结果表明COA-Cl在ICH中具有神经保护作用。此外,我们的研究提供了证据表明COA-Cl可能减轻氧化应激,这可能是其神经保护作用的潜在机制之一。

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