Collaço-Moraes Y, Aspey B S, de Belleroche J S, Harrison M J
Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
Stroke. 1994 Sep;25(9):1855-60; discussion 1861. doi: 10.1161/01.str.25.9.1855.
There is strong evidence to implicate glutamate in the cerebral damage caused by ischemia. In this study we investigated the role of glutamate receptors in mediating effects of middle cerebral artery occlusion (MCAO) on immediate early gene expression in the rat by quantitation of mRNA levels.
The effect of MCAO on the induction of immediate early genes was studied in five regions, both ipsilateral and contralateral to the occlusion: the "core" ischemic area of the cortex in the central region of the middle cerebral artery territory, the surrounding area, frontal cortex, occipital cortex, and hippocampus. Levels of c-fos, c-jun, zif-268, and krox-20 mRNA were measured by Northern and slot blot analysis.
A large induction of c-fos mRNA was obtained in all four cortical regions ipsilateral to the occlusion, with the greatest effect detected in the core area. Little effect was detected in the ipsilateral hippocampus and in all contralateral regions. Pretreatment with MK-801 (3 mg/kg) largely inhibited the induction of c-fos mRNA, indicating that the induction was mediated through an N-methyl-D-aspartate subtype of glutamate receptor. MCAO also produced a significant induction of c-jun and zif-268 mRNA in ipsilateral cortical regions.
These results indicate that MCAO causes a profound modulation of the expression of multiple genes in an extensive area of cerebral cortex extending beyond the immediate area supplied by the middle cerebral artery. The marked effect of MK-801 indicates the potential importance of glutamate antagonists in restricting the widespread deleterious effects of glutamate.
有充分证据表明谷氨酸与缺血所致脑损伤有关。在本研究中，我们通过定量mRNA水平来研究谷氨酸受体在介导大脑中动脉闭塞（MCAO）对大鼠即刻早期基因表达影响中的作用。
在闭塞同侧和对侧的五个区域研究MCAO对即刻早期基因诱导的影响：大脑中动脉供血区域中央部分皮质的“核心”缺血区、周边区域、额叶皮质、枕叶皮质和海马体。通过Northern印迹和狭缝印迹分析测量c-fos、c-jun、zif-268和krox-20 mRNA的水平。
在闭塞同侧的所有四个皮质区域均观察到c-fos mRNA的大量诱导，其中核心区域的影响最大。在同侧海马体和所有对侧区域未检测到明显影响。用MK-801（3 mg/kg）预处理可大大抑制c-fos mRNA的诱导，表明该诱导是通过谷氨酸受体的N-甲基-D-天冬氨酸亚型介导的。MCAO还在同侧皮质区域显著诱导了c-jun和zif-268 mRNA。
这些结果表明，MCAO可导致大脑皮质广泛区域内多个基因表达的深刻调节，该区域超出了大脑中动脉直接供血的区域。MK-801的显著作用表明谷氨酸拮抗剂在限制谷氨酸广泛有害作用方面的潜在重要性。
