Tanaka Ai, Ito Yasuo, Kawasaki Hitoshi, Kitabayashi Chika, Nishioka Ryoji, Yamazato Masamizu, Ishizawa Keisuke, Nagai Toshinori, Hirayama Makiko, Takahashi Kazushi, Yamamoto Toshimasa, Araki Nobuo
Department of Neurology, Saitama Medical University, Moroyama, Saitama, Japan; Department of Neurology, Tottori Medical Center, Tottori, Japan.
Department of Neurology, Saitama Medical University, Moroyama, Saitama, Japan.
J Stroke Cerebrovasc Dis. 2018 Jun;27(6):1609-1615. doi: 10.1016/j.jstrokecerebrovasdis.2018.01.014.
The purpose of this study was to investigate the effects of memantine on brain ischemia. Because we can measure nitric oxide (NO) production and hydroxyl radical metabolism continuously, we investigated the effect of memantine on NO production and hydroxyl radical metabolism in cerebral ischemia and reperfusion.
Memantine (25 µmol/kg) was administered intraperitoneally to 6 C57BL/6 mice 30 minutes before ischemia. Seven additional mice received no injection (controls). NO production and hydroxyl radical metabolism were continuously monitored using bilateral striatal microdialysis in vivo. Hydroxyl radical formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by occluding the common carotid artery bilaterally for 10 minutes. Levels of the NO metabolites nitrite (NO) and nitrate (NO) were determined using the Griess reaction. Survival rates of hippocampal CA1 neurons were calculated and 8-hydroxydeoxyguanosine (8-OHdG)-immunopositive cells were counted to evaluate the oxidative stress in hippocampal CA1 neurons 72 hours after the start of reperfusion.
The regional cerebral blood flow was significantly higher in the memantine group than in the control group after reperfusion. Furthermore, the level of 2,3-dihydroxybenzoic acid was significantly lower in the memantine group than in the control group during ischemia and reperfusion. Levels of NO and NO did not differ significantly between the 2 groups. Although survival rates in the CA1 did not differ significantly, there were fewer 8-OHdG-immunopositive cells in animals that had received memantine than in control animals.
These data suggest that memantine exerts partially neuroprotective effects against cerebral ischemic injury.
本研究旨在探讨美金刚对脑缺血的影响。由于我们能够连续测量一氧化氮（NO）生成和羟自由基代谢，因此研究了美金刚对脑缺血再灌注时NO生成和羟自由基代谢的影响。
在缺血前30分钟，对6只C57BL/6小鼠腹腔注射美金刚（25 μmol/kg）。另外7只小鼠不注射（作为对照）。采用双侧纹状体微透析在体连续监测NO生成和羟自由基代谢。采用水杨酸捕获法监测羟自由基的形成。通过双侧阻断颈总动脉10分钟，使所有小鼠发生前脑缺血。采用Griess反应测定NO代谢产物亚硝酸盐（NO）和硝酸盐（NO）的水平。计算海马CA1神经元的存活率，并对8-羟基脱氧鸟苷（8-OHdG）免疫阳性细胞进行计数，以评估再灌注开始72小时后海马CA1神经元的氧化应激情况。
再灌注后，美金刚组的局部脑血流量显著高于对照组。此外，在缺血和再灌注期间，美金刚组的2,3-二羟基苯甲酸水平显著低于对照组。两组之间NO和NO的水平无显著差异。虽然CA1区的存活率无显著差异，但接受美金刚治疗的动物中8-OHdG免疫阳性细胞比对照动物少。
这些数据表明，美金刚对脑缺血损伤具有部分神经保护作用。
