鸟氨酸脱羧酶基因敲低会加剧大鼠脑内短暂性局灶性脑缺血诱导的神经元损伤。

Ornithine decarboxylase knockdown exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain.

作者信息

Raghavendra Rao V L, Dogan A, Bowen K K, Dempsey R J

机构信息

Department of Neurological Surgery, Cardiovascular Research Center, University of Wisconsin-Madison 53792, USA.

出版信息

J Cereb Blood Flow Metab. 2001 Aug;21(8):945-54. doi: 10.1097/00004647-200108000-00007.

DOI:10.1097/00004647-200108000-00007

PMID:11487730

Abstract

Transient cerebral ischemia leads to increased expression of ornithine decarboxylase (ODC). Contradicting studies attributed neuroprotective and neurotoxic roles to ODC after ischemia. Using antisense oligonucleotides (ODNs), the current study evaluated the functional role of ODC in the process of neuronal damage after transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Transient MCAO significantly increased the ODC immunoreactive protein levels and catalytic activity in the ipsilateral cortex, which were completely prevented by the infusion of antisense ODN specific for ODC. Transient MCAO in rats infused with ODC antisense ODN increased the infarct volume, motor deficits, and mortality compared with the sense or random ODN-infused controls. Results of the current study support a neuroprotective or recovery role, or both, for ODC after transient focal ischemia.

摘要

短暂性脑缺血会导致鸟氨酸脱羧酶（ODC）表达增加。相互矛盾的研究将缺血后ODC的神经保护和神经毒性作用归因于此。本研究使用反义寡核苷酸（ODN），评估了ODC在自发性高血压大鼠大脑中动脉闭塞（MCAO）诱导的短暂性局灶性脑缺血后神经元损伤过程中的功能作用。短暂性MCAO显著增加了同侧皮质中ODC免疫反应性蛋白水平和催化活性，而注入针对ODC的反义ODN可完全阻止这种增加。与注入正义或随机ODN的对照组相比，注入ODC反义ODN的大鼠短暂性MCAO增加了梗死体积、运动功能缺陷和死亡率。本研究结果支持ODC在短暂性局灶性缺血后具有神经保护或恢复作用，或两者兼具。