Glibenclamide Prevents Water Diffusion Abnormality in the Brain After Cardiac Arrest in Rats
Glibenclamide Prevents Water Diffusion Abnormality in the Brain After Cardiac Arrest in Rats
复制标题
格列本脲可防止大鼠心脏骤停后大脑中的水扩散异常
DOI：
10.1007/s12028-018-0505-0
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Wu, Yongming
中科院分区：
文献类型：
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作者：
Huang, Kaibin;Wang, Ziyue;Wu, Yongming
格列本脲（GBC）可改善大鼠心脏骤停（CA）后的神经功能结局。在本研究中，我们试图通过使用高场磁共振成像系统来阐明GBC发挥神经保护作用的机制。
雄性Sprague - Dawley大鼠经历10分钟窒息性心脏骤停，随后进行心肺复苏（CPR）。在心脏骤停前以及复苏后24小时、48小时和72小时分别进行弥散加权成像（DWI）以及传统的T2加权成像。之后，进行组织学检查。
12只大鼠在自主循环恢复后15分钟随机接受GBC（n = 6）或赋形剂（n = 6），同时将4只大鼠设为假手术对照组。经历心脏骤停/心肺复苏并接受赋形剂的大鼠表现出明显的神经功能缺损，而GBC治疗可减轻这种缺损。心脏骤停/心肺复苏后，在大脑易损区域检测到明显的水弥散异常，表现为DWI高信号，在72小时时海马CA1区的DWI高信号最为突出。同样，组织学检查显示，接受赋形剂治疗的大鼠海马CA1区存在神经元肿胀、树突损伤以及星形胶质细胞和小胶质细胞激活。相关性分析表明，海马区的表观弥散系数（ADC）值与组织学结果显著相关（所有p均<0.05）。
这些结果表明，GBC在心脏骤停后发挥神经保护作用，至少部分是通过防止水弥散异常即脑水肿来实现的。
Glibenclamide (GBC) improves neurological outcome after cardiac arrest (CA) in rats. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of GBC by using a high-field MRI system.Male Sprague-Dawley rats were subjected to 10-min asphyxial CA followed by cardiopulmonary resuscitation (CPR). Diffusion-weighted imaging (DWI) as well as conventional T2-weighted imaging was conducted prior to CA and at 24, 48, and 72 h after resuscitation. Afterward, histological examination was performed.Twelve rats were randomized to receive GBC (n = 6) or vehicle (n = 6) at 15 min after return of spontaneous circulation, while four rats were set as sham control. Rats that underwent CA/CPR and received vehicle exhibited distinct neurological deficit, which was alleviated by GBC treatment. Marked water diffusion abnormality as demonstrated by hyperintense DWI in vulnerable regions of the brain was detected after CA/CPR, with the most prominent hyperintense DWI observed in the hippocampal CA1 region at 72 h. Consistently, histological examination revealed neuronal swelling, dendritic injury, and activation of astrocytes and microglia in the hippocampal CA1 region in vehicle-treated rats. Correlation analysis revealed that the ADC values in the hippocampus were significantly correlated with the histological findings (all p < 0.05).These results suggest that the neuroprotective effects of GBC after CA was exerted, as least in part, through prevention of water diffusion abnormality, namely brain edema.