Institute of Molecular Genetics of National Research Center "Kurchatov Institute", Kurchatov Sq. 2, Moscow 123182, Russia.
Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, Russia.
Genes (Basel). 2023 Jun 30;14(7):1382. doi: 10.3390/genes14071382.
Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) when effective treatment can be provided. Here, we used a transient middle cerebral artery occlusion (tMCAO) model in rats to study two synthetic derivatives of adrenocorticotropic hormone (ACTH). The first was ACTH(4-7)PGP, which is known as Semax. It is actively used as a neuroprotective drug. The second was the ACTH(6-9)PGP peptide, which is elucidated as a prospective agent only. Using RNA-Seq analysis, we revealed hundreds of ischemia-related differentially expressed genes (DEGs), as well as 131 and 322 DEGs related to the first and second peptide at 4.5 h after tMCAO, respectively, in dorsolateral areas of the frontal cortex of rats. Furthermore, we showed that both Semax and ACTH(6-9)PGP can partially prevent changes in the immune- and neurosignaling-related gene expression profiles disturbed by the action of ischemia at 4.5 h after tMCAO. However, their different actions with regard to predominantly immune-related genes were also revealed. This study gives insight into how the transcriptome depends on the variation in the structure of the related peptides, and it is valuable from the standpoint of the development of measures for early post-stroke therapy.
缺血性中风是由于血栓或栓子导致的急性局部脑血流减少。特别重要的是研究决定形成和维持治疗窗（中风后长达 6 小时的时间间隔）的遗传系统的机制，在此期间可以提供有效的治疗。在这里，我们使用大鼠短暂性大脑中动脉闭塞（tMCAO）模型来研究两种合成促肾上腺皮质激素（ACTH）衍生物。第一个是 ACTH(4-7)PGP，称为 Semax。它被积极用作神经保护药物。第二个是 ACTH(6-9)PGP 肽，仅被阐明为潜在的药物。使用 RNA-Seq 分析，我们在 tMCAO 后 4.5 小时分别在大鼠额皮质背外侧区域中揭示了数百个与缺血相关的差异表达基因（DEG），以及与第一个和第二个肽相关的 131 和 322 个 DEG。此外，我们表明，在 tMCAO 后 4.5 小时，Semax 和 ACTH(6-9)PGP 均可部分预防与缺血作用相关的免疫和神经信号相关基因表达谱的变化。然而，它们在主要与免疫相关的基因上的不同作用也被揭示出来。这项研究深入了解了转录组如何依赖于相关肽结构的变化，并且从早期中风治疗措施的发展角度来看具有价值。
