Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Section of Neurosurgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC.
J Clin Neurol. 2014 Apr;10(2):84-93. doi: 10.3988/jcn.2014.10.2.84. Epub 2014 Apr 23.
Hypoxia, or ischemia, is a common cause of neurological deficits in the elderly. This study elucidated the mechanisms underlying ischemia-induced brain injury that results in neurological sequelae.
Cerebral ischemia was induced in male Sprague-Dawley rats by transient ligation of the left carotid artery followed by 60 min of hypoxia. A two-dimensional differential proteome analysis was performed using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to compare changes in protein expression on the lesioned side of the cortex relative to that on the contralateral side at 0, 6, and 24 h after ischemia.
The expressions of the following five proteins were up-regulated in the ipsilateral cortex at 24 h after ischemia-reperfusion injury compared to the contralateral (i.e., control) side: aconitase 2, neurotensin-related peptide, hypothetical protein XP-212759, 60-kDa heat-shock protein, and aldolase A. The expression of one protein, dynamin-1, was up-regulated only at the 6-h time point. The level of 78-kDa glucose-regulated protein precursor on the lesioned side of the cerebral cortex was found to be high initially, but then down-regulated by 24 h after the induction of ischemia-reperfusion injury. The expressions of several metabolic enzymes and translational factors were also perturbed soon after brain ischemia.
These findings provide insights into the mechanisms underlying the neurodegenerative events that occur following cerebral ischemia.
缺氧或缺血是老年人发生神经功能缺损的常见原因。本研究阐明了导致缺血性脑损伤从而产生神经后遗症的机制。
通过短暂结扎左侧颈总动脉并随后进行 60 分钟缺氧，在雄性 Sprague-Dawley 大鼠中诱导脑缺血。采用基质辅助激光解吸电离飞行时间质谱进行二维差异蛋白质组分析，以比较缺血后 0、6 和 24 小时时损伤侧皮质相对于对侧的蛋白质表达变化。
与对侧（即对照侧）相比，缺血再灌注损伤后 24 小时，同侧皮质中以下五种蛋白质的表达上调：乌头酸酶 2、神经降压素相关肽、假定蛋白 XP-212759、60kDa 热休克蛋白和醛缩酶 A。一种蛋白质，即动力蛋白 1，仅在 6 小时时间点上调。大脑皮质损伤侧的 78kDa 葡萄糖调节蛋白前体的水平最初较高，但在诱导缺血再灌注损伤后 24 小时下降。几种代谢酶和翻译因子的表达也在脑缺血后很快受到干扰。
这些发现为缺血性脑损伤后发生的神经退行性事件的机制提供了深入的了解。
