Institute of Neuroanatomy, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
Department of Neurology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2021 Dec 23;23(1):161. doi: 10.3390/ijms23010161.
Ischemic stroke is characterized by an occlusion of a cerebral blood vessel resulting in neuronal cell death due to nutritional and oxygen deficiency. Additionally, post-ischemic cell death is augmented after reperfusion. These events are paralleled by dysregulated miRNA expression profiles in the peri-infarct area. Understanding the underlying molecular mechanism in the peri-infarct region is crucial for developing promising therapeutics. Utilizing a tMCAo (transient Middle Cerebral Artery occlusion) model in rats, we studied the expression levels of the miRNAs (miR) 223-3p, 155-5p, 3473, and 448-5p in the cortex, amygdala, thalamus, and hippocampus of both the ipsi- and contralateral hemispheres. Additionally, the levels in the blood serum, spleen, and liver and the expression of their target genes, namely, , , , and , were assessed. We observed an increase in all miRNAs on the ipsilateral side of the cerebral cortex in a time-dependent manner and increased miRNAs levels (miR-223-3p, miR-3473, and miR-448-5p) in the contralateral hemisphere after 72 h. Besides the cerebral cortex, the amygdala presented increased expression levels, whereas the thalamus and hippocampus showed no alterations. Different levels of the investigated miRNAs were detected in blood serum, liver, and spleen. The gene targets were altered not only in the peri-infarct area of the cortex but selectively increased in the investigated non-affected brain regions along with the spleen and liver during the reperfusion time up to 72 h. Our results suggest a supra-regional influence of miRNAs following ischemic stroke, which should be studied to further identify whether miRNAs are transported or locally upregulated.
缺血性脑卒中的特征是脑血管阻塞，导致神经元细胞因营养和氧气缺乏而死亡。此外，再灌注后会加剧缺血后细胞死亡。这些事件与梗塞周围区域失调的 miRNA 表达谱平行。了解梗塞周围区域的潜在分子机制对于开发有前途的治疗方法至关重要。我们利用大鼠的 tMCAo（短暂性大脑中动脉闭塞）模型，研究了 miRNA（miR）223-3p、155-5p、3473 和 448-5p 在大脑皮质、杏仁核、丘脑和海马体的同侧和对侧半球中的表达水平。此外，还评估了血清、脾脏和肝脏中的水平以及它们的靶基因的表达，即 、 、 、 和 。我们观察到所有 miRNA 在大脑皮质的同侧以时间依赖性方式增加，并且在 72 小时后对侧半球的 miRNA 水平（miR-223-3p、miR-3473 和 miR-448-5p）增加。除了大脑皮质外，杏仁核也呈现出表达水平增加，而丘脑和海马体则没有变化。在血清、肝脏和脾脏中检测到不同水平的研究 miRNA。靶基因不仅在大脑皮质梗塞周围区域发生改变，而且在再灌注期间，包括脾脏和肝脏在内的未受影响的脑区选择性增加，直到 72 小时。我们的结果表明，缺血性脑卒中后存在 miRNA 的超区域影响，应该进一步研究以确定 miRNA 是否被运输或局部上调。
