Centro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira Interior, Covilhã, Portugal.
Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal.
J Neurosci Res. 2021 May;99(5):1414-1432. doi: 10.1002/jnr.24792. Epub 2021 Feb 1.
After decades of effort, there are no effective clinical treatments to induce the recovery of ischemia-injured tissues, and among the several strategies that have been explored, repetitive transcranial magnetic stimulation has proven to be one of the most promising, with beneficial effects in limb motor function, aphasia, hemispatial neglect, or dysphagia. Despite the clinical evidences, little is known about the mechanisms underlying those effects. The present study aimed to explore the cellular and molecular effects of high-frequency repetitive magnetic stimulation (HF-rMS) on an in vitro model of ischemia. Using primary cortical cultures exposed to oxygen and glucose deprivation followed by reperfusion, we observed that HF-rMS treatment prevents the ischemia-induced neuronal death by 21.2%, and the neurite degeneration triggered by ischemia. Our results also demonstrate that with this treatment there is an increase of 89.2% on the number cells expressing ERK1/2, of 20.1% on the number of cells expressing c-Fos, and a synaptogenic effect, through an increase of 62.9% in the number of synaptic puncta as well as of 49.4% in their intensity. Interestingly, our results indicate that astrocytes are crucial to the beneficial effects triggered by HF-rMS after ischemia, thus suggesting a direct effect of HF-rMS on these cells. The modulation of astrocytes with this non-invasive brain stimulation technique is a promising approach to promote the recovery of ischemia-induced injured tissues; however, it is essential to understand how these effects can be modulated in order to optimize the protocols and enhance the beneficial outcomes.
经过几十年的努力，目前尚无有效的临床治疗方法来诱导缺血性损伤组织的恢复，在探索的几种策略中，重复经颅磁刺激已被证明是最有前途的策略之一，对肢体运动功能、失语症、半空间忽略或吞咽困难有有益的影响。尽管有临床证据，但对于这些影响的机制知之甚少。本研究旨在探索高频重复磁刺激（HF-rMS）对体外缺血模型的细胞和分子影响。使用暴露于缺氧和葡萄糖剥夺后再灌注的原代皮质培养物，我们观察到 HF-rMS 治疗可将缺血引起的神经元死亡减少 21.2%，并防止缺血引起的神经突退化。我们的结果还表明，经过这种治疗，表达 ERK1/2 的细胞数量增加了 89.2%，表达 c-Fos 的细胞数量增加了 20.1%，并具有突触生成作用，通过增加 62.9%的突触突数量和 49.4%的突触突强度。有趣的是，我们的结果表明，星形胶质细胞对于 HF-rMS 在缺血后引发的有益作用至关重要，这表明 HF-rMS 对这些细胞有直接作用。用这种非侵入性脑刺激技术调节星形胶质细胞是促进缺血性损伤组织恢复的有前途的方法；然而，了解如何调节这些作用以优化方案并增强有益结果至关重要。
