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

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• 作者：Feng Lu ; PhD^* ; Takehiro Nakamura ; MD ; PhD^&dagger ; ; ^{tanakamu@kms.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Naohiko Okabe ; MD ; PhD^* ; Naoyuki Himi ; PhD^* ; Emi Nakamura-Maruyama ; PhD^* ; Takashi Shiromoto ; MD^* ; Kazuhiko Narita ; PhD^* ; Ikuko Tsukamoto ; PhD^&Dagger ; ; Guohua Xi ; MD^§ ; ; Richard F. Keep ; PhD^§ ; ; Osamu Miyamoto ; MD ; PhD^*
• 关键词：Intracerebral hemorrhage ; adenosine analog ; neuroprotection ; rat
• 刊名：Journal of Stroke and Cerebrovascular Diseases
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：25
• 期：11
• 页码：2637-2643
• 全文大小：986 K

文摘

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.