Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, 10000, Zagreb, Croatia.
Universität Zürich, Universitätspital Zürich, Zürich, Switzerland.
Sci Rep. 2023 May 26;13(1):8539. doi: 10.1038/s41598-023-35515-8.
The aim of this study was to characterize expression of corticogenesis-related transcription factors BCL11B and SATB2 after brain ischemic lesion in the adult mice, and to analyze their correlation to the subsequent brain recovery. Ischemic brain lesion was induced by transient middle cerebral artery occlusion followed by reperfusion, and the animals with ischemic lesion were compared to the sham controls. Progression of the brain damage and subsequent recovery was longitudinally monitored structurally, by magnetic resonance imaging, and functionally, by neurological deficit assessment. Seven days after the ischemic injury the brains were isolated and analyzed by immunohistochemistry. The results showed higher expression in the brain of both, BCL11B and SATB2 in the animals with ischemic lesion compared to the sham controls. The co-expression of both markers, BCL11B and SATB2, increased in the ischemic brains, as well as the co-expression of BCL11B with the beneficial transcriptional factor ATF3 but not its co-expression with detrimental HDAC2. BCL11B was mainly implicated in the ipsilateral and SATB2 in the contralateral brain hemisphere, and their level in these regions correlated with the functional recovery rate. The results indicate that the reactivation of corticogenesis-related transcription factors BCL11B and SATB2 is beneficial after brain ischemic lesion.
本研究旨在探讨脑缺血损伤后皮质生成相关转录因子 BCL11B 和 SATB2 的表达特征，并分析其与随后的脑恢复之间的相关性。通过短暂性大脑中动脉闭塞再灌注诱导脑缺血损伤，将缺血损伤动物与假手术对照进行比较。采用磁共振成像进行结构纵向监测，采用神经功能缺损评估进行功能纵向监测，以跟踪脑损伤的进展和随后的恢复。缺血损伤后 7 天，分离大脑并通过免疫组织化学进行分析。结果显示，与假手术对照组相比，缺血损伤动物的大脑中 BCL11B 和 SATB2 的表达水平更高。两种标志物 BCL11B 和 SATB2 的共表达增加，以及有益转录因子 ATF3 与 BCL11B 的共表达，但与有害的 HDAC2 没有共表达。BCL11B 主要与同侧脑区相关，SATB2 主要与对侧脑区相关，这些区域的表达水平与功能恢复率相关。研究结果表明，脑缺血损伤后皮质生成相关转录因子 BCL11B 和 SATB2 的再激活是有益的。
