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大鼠局灶性脑缺血再灌注亚急性期单侧大脑半球的神经化学变化:一项离体氢磁共振波谱研究

Neurochemical changes in unilateral cerebral hemisphere during the subacute stage of focal cerebral ischemia-reperfusion in rats: An ex vivo H magnetic resonance spectroscopy study.

作者信息

Huang Qun, Li Chen, Xia Nengzhi, Zhao Liangcai, Wang Dan, Yang Yunjun, Gao Hongchang

机构信息

Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

出版信息

Brain Res. 2018 Apr 1;1684:67-74. doi: 10.1016/j.brainres.2018.01.026. Epub 2018 Feb 1.

DOI:10.1016/j.brainres.2018.01.026
PMID:29408682
Abstract

Understanding the subacute may shed light on the mechanism of cerebral ischemia. The present study aimed to explore metabolic features underlying subacute stage of ischemia-reperfusion injury and developing effective treatments. Rats were divided into three groups: the permanent middle cerebral artery occlusion (pMCAO), transient cerebral focal ischemia (tMCAO) and sham group. Evaluation of animal models was performed by the neurological deficit, MR images and pathological morphological abnormality. To elucidate metabolic changes, we conducted a comparative analysis of metabolic composition of unilateral brain tissue using H nuclear magnetic resonance spectroscopy. The successful model was observed low signal on T1WI and high signal on T2WI lesions in the left cerebral. Histopathological results confirmed the formation of apparent lesions in the left striatum, hippocampus CA1 and cortex tissues of subacute cerebral ischemia rats and showed that rats with focal cerebral ischemia-reperfusion could alleviate the extent of pathological damage degree. In pMCAO rats 7 days after surgery, decreased levels of N-acetyl aspartate (NAA), γ-aminobutyric acid (GABA), glutamate (Glu) and succinate (Suc) concomitantly with increased levels of glutamine (Gln), myo-inositol (m-Ins) and lactate (Lac) were observed compared to the control. Whereas, increased level of Lac with decreased levels of NAA, GABA, Glu, Suc, creatine (Cre) were observed in the tMCAO rats. This demonstrated that experimental subacute ischemic stroke in rats caused extensive perturbation in energy metabolism, the tricarboxylic acid cycle and GABA shunt, which provided essential information for understanding the pathogenesis of subacute cerebral ischemia-reperfusion and provided guidance in choosing the suitable therapeutic schedule.

摘要

了解亚急性期可能有助于揭示脑缺血的机制。本研究旨在探讨缺血再灌注损伤亚急性期的代谢特征并开发有效的治疗方法。将大鼠分为三组:永久性大脑中动脉闭塞组(pMCAO)、短暂性脑局灶性缺血组(tMCAO)和假手术组。通过神经功能缺损、磁共振图像和病理形态学异常对动物模型进行评估。为了阐明代谢变化,我们使用氢核磁共振波谱对单侧脑组织的代谢成分进行了比较分析。成功的模型在左侧大脑T1WI上观察到低信号,T2WI上观察到高信号病变。组织病理学结果证实亚急性脑缺血大鼠左侧纹状体、海马CA1和皮质组织中形成明显病变,并表明局灶性脑缺血再灌注大鼠可减轻病理损伤程度。与对照组相比,在pMCAO大鼠术后7天,观察到N-乙酰天门冬氨酸(NAA)、γ-氨基丁酸(GABA)、谷氨酸(Glu)和琥珀酸(Suc)水平降低,同时谷氨酰胺(Gln)、肌醇(m-Ins)和乳酸(Lac)水平升高。然而,在tMCAO大鼠中观察到Lac水平升高,而NAA、GABA、Glu、Suc、肌酸(Cre)水平降低。这表明大鼠实验性亚急性缺血性中风导致能量代谢、三羧酸循环和GABA分流广泛紊乱,这为理解亚急性脑缺血再灌注的发病机制提供了重要信息,并为选择合适的治疗方案提供了指导。

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