Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany.
Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.
Int J Mol Sci. 2023 Jul 25;24(15):11893. doi: 10.3390/ijms241511893.
Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have not yet been investigated in the ischemic brain. Applying immunofluorescence labeling, this study explored tricellulin, MFAP5 and α-catenin in non-ischemic and ischemic brain areas of mice (24, 4 h of ischemia) and rats (4 h of ischemia), along with collagen IV and fibronectin as vascular and extracellular matrix constituents and microtubule-associated protein 2 (MAP2) and neurofilament light chain (NF-L) as cytoskeletal elements. Immunosignals of tricellulin and notably MFAP5 partially appeared in a fiber-like pattern, and α-catenin appeared more in a dotted pattern. Regional associations with vascular and extracellular constituents were found for tricellulin and α-catenin, particularly in ischemic areas. Due to ischemia, signals of tricellulin, MFAP5 and α-catenin decreased concomitantly with MAP2 and NF-L, whereby MFAP5 provided the most sensitive reaction. For the first time, this study demonstrated ischemia-related alterations in tricellulin, MFAP5 and α-catenin along with the vasculature, extracellular matrix and cytoskeleton. Confirmatory studies are needed, also exploring their role in cellular integrity and the potential for neuroprotective approaches in stroke.
除了深入了解中风的病理生理学和寻找神经保护靶点的举措外,稳定细胞的元素也引起了越来越多的关注。虽然细胞培养实验表明三叶肽聚糖、α-连环蛋白和微纤维相关蛋白 5(MFAP5)有助于细胞完整性,但这些元素在缺血性大脑中尚未得到研究。本研究应用免疫荧光标记法,研究了非缺血和缺血小鼠(24 小时和 4 小时缺血)及大鼠(4 小时缺血)脑区的三叶肽聚糖、MFAP5 和α-连环蛋白,以及作为血管和细胞外基质成分的胶原蛋白 IV 和纤维连接蛋白,以及微管相关蛋白 2(MAP2)和神经丝轻链(NF-L)作为细胞骨架成分。三叶肽聚糖和 MFAP5 的免疫信号部分呈纤维状,而α-连环蛋白则呈点状。三叶肽聚糖和α-连环蛋白与血管和细胞外成分的区域关联在缺血区尤为明显。由于缺血,三叶肽聚糖、MFAP5 和α-连环蛋白的信号与 MAP2 和 NF-L 同时下降,其中 MFAP5 的反应最敏感。本研究首次证明了缺血相关的三叶肽聚糖、MFAP5 和α-连环蛋白与血管、细胞外基质和细胞骨架的改变。需要进行确认性研究,也探索它们在细胞完整性中的作用以及在中风中神经保护方法的潜力。