Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon F-21078, France.
Neuroscience. 2013 Feb 12;231:169-81. doi: 10.1016/j.neuroscience.2012.11.054. Epub 2012 Dec 7.
Stroke is a leading cause of death and disability in industrialized countries. Although surviving patients exhibit a certain degree of restoration of function attributable to brain plasticity, the majority of stroke survivors has to struggle with persisting deficits. In order to potentiate post-stroke recovery, several rehabilitation therapies have been undertaken and many experimental studies have reported that brain-derived neurotrophic factor (BDNF) is central to many facets of neuroplastic processes. However, although BDNF role in brain plasticity is well characterized through strategies that manipulate its content, the involvement of this neurotrophin in spontaneous post-stroke recovery remains to be clarified. Besides, while the neuroplastic role of BDNF is restricted to its mature form, most studies investigating the proper effect of ischemia on post-stroke BDNF metabolism focused on mRNA or total protein expressions. In addition, these studies are mainly performed in brain regions collected either at or around the lesion site. Therefore, the objective of the present study was to investigate in both hemispheres, the long-term expression (up to one month) of both pro- and mature BDNF forms in rats subjected to photothrombotic ischemia. These assessments were performed in the cortex and in the hippocampus, two regions known to subserve functional recovery after stroke and were coupled to the study of synaptophysin expression, a marker of synaptogenesis. Our study reports that stroke induces an early and transient increase (4h) in mature BDNF expression in the cortex of both hemispheres that was associated with a delayed rise (30d) in synaptophysin levels ipsilateraly. In both hippocampal territories, the pattern of mature BDNF expression shows a more delayed increase (from 8 to 30d), which coincides with the evolution of synaptophysin expression. Interestingly, in these hippocampal territories, pro-BDNF levels evolve differently suggesting a differential gene regulation between the two hemispheres. While highlighting the complexity of changes in BDNF metabolism after stroke, our data suggest that BDNF involvement in spontaneous post-stroke plasticity is region-dependent.
中风是工业化国家死亡和残疾的主要原因。尽管幸存的患者表现出一定程度的功能恢复归因于大脑可塑性，但大多数中风幸存者都在与持续的缺陷作斗争。为了增强中风后的恢复，已经采用了几种康复治疗方法，许多实验研究报告脑源性神经营养因子（BDNF）是神经可塑性过程的许多方面的核心。然而，尽管通过操纵其含量的策略对 BDNF 在大脑可塑性中的作用进行了很好的描述，但这种神经营养因子在自发性中风后恢复中的作用仍有待阐明。此外，虽然 BDNF 的神经可塑性作用仅限于其成熟形式，但大多数研究缺血对中风后 BDNF 代谢的适当影响的研究主要集中在 mRNA 或总蛋白表达上。此外，这些研究主要在病变部位或其周围采集的脑区进行。因此，本研究的目的是在光血栓性缺血大鼠的两个半球中研究前体和成熟 BDNF 形式的长期表达（长达一个月）。这些评估在皮质和海马体中进行，这两个区域已知在中风后具有功能恢复作用，并与突触小体蛋白表达的研究相结合，突触小体蛋白是突触发生的标志物。我们的研究报告表明，中风会导致两侧皮质中成熟 BDNF 表达的早期和短暂增加（4 小时），这种增加与同侧突触小体蛋白水平的延迟增加（30 天）有关。在两个海马区，成熟 BDNF 表达模式显示出更延迟的增加（从 8 天到 30 天），这与突触小体蛋白表达的演变相吻合。有趣的是，在这些海马区，前体 BDNF 水平的变化不同，表明两个半球之间的基因调控存在差异。我们的数据表明，BDNF 参与自发性中风后可塑性是区域依赖性的，同时强调了中风后 BDNF 代谢变化的复杂性。
