Rangel Y M, Karikó K, Harris V A, Duvall M E, Welsh F A
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6070, USA.
Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):103-12. doi: 10.1016/s0169-328x(01)00037-7.
Previous studies have demonstrated that cortical spreading depression (CSD) increases the expression of putative neuroprotective proteins. The objective of the present study was to elucidate the relationship between the number of episodes of CSD and steady-state levels of mRNAs encoding brain-derived neurotrophic factor (BDNF), heat-shock protein-72 (hsp72) and c-fos. Wistar rats were administered one, five, or twenty-five episodes of CSD evoked by application of 2 M KCl to the frontal cortex of one hemisphere. Animals were permitted to recover for 30 min, 2 h or 24 h prior to sacrifice. Total RNA was isolated from the parietal cortex of each hemisphere and analyzed using Northern blots. At 30 min recovery, levels of BDNF mRNA were not significantly elevated after 1 episode of CSD, but were increased 4-fold after five episodes of CSD and 11-fold after twenty-five episodes of CSD, relative to levels in the contralateral hemisphere. At 2 h recovery, BDNF mRNA levels increased 2-, 3- and 9-fold, respectively. At 24 h, BDNF mRNA had returned to control levels in all groups. Thus, CSD increased levels of BDNF mRNA in a dose-dependent fashion at the early recovery times. Hsp72 mRNA was below the level of detection after 1 and 5 episodes of CSD. However, after twenty-five episodes of CSD, hsp72 mRNA levels were increased in the ipsilateral hemisphere at 30 min and 2 h recovery. Unlike levels of BDNF and hsp72 mRNA, levels of c-fos mRNA were increased nearly to the same extent at 30 min and 2 h after one, five or twenty-five episodes of CSD before returning to control by 24 h recovery. These results demonstrate that CSD triggers a dose-dependent increase in the expression of genes encoding neuroprotective proteins, which may mediate tolerance to ischemia induced by CSD.
先前的研究表明，皮层扩散性抑制（CSD）可增加假定的神经保护蛋白的表达。本研究的目的是阐明CSD发作次数与编码脑源性神经营养因子（BDNF）、热休克蛋白72（hsp72）和c-fos的mRNA稳态水平之间的关系。向Wistar大鼠一侧半球的额叶皮层施加2 M KCl，诱发1次、5次或25次CSD。在处死前，让动物恢复30分钟、2小时或24小时。从每个半球的顶叶皮层分离总RNA，并使用Northern印迹法进行分析。恢复30分钟时，相对于对侧半球，1次CSD发作后BDNF mRNA水平未显著升高，但5次CSD发作后升高了4倍，25次CSD发作后升高了11倍。恢复2小时时，BDNF mRNA水平分别升高了2倍、3倍和9倍。在24小时时，所有组的BDNF mRNA均恢复到对照水平。因此，在早期恢复阶段，CSD以剂量依赖的方式增加BDNF mRNA水平。1次和5次CSD发作后，hsp72 mRNA低于检测水平。然而，25次CSD发作后，在恢复30分钟和2小时时，同侧半球的hsp72 mRNA水平升高。与BDNF和hsp72 mRNA水平不同，1次、5次或25次CSD发作后30分钟和2小时，c-fos mRNA水平升高的程度几乎相同，在恢复24小时后恢复到对照水平。这些结果表明，CSD触发了编码神经保护蛋白的基因表达的剂量依赖性增加，这可能介导了对CSD诱导的缺血的耐受性。
