Ishizuka Kentaro, Saito Moeko, Shibata Noriyuki, Kitagawa Kazuo
Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Neurosci Res. 2023 May;190:85-91. doi: 10.1016/j.neures.2022.11.005. Epub 2022 Nov 12.
MRI diffusion-weighted imaging (DWI)-FLAIR mismatch is known as predictive of symptom onset within 4.5 h. This study assessed the breakdown of cytoskeletal protein and blood-brain barrier (BBB) in DWI-T2 mismatch. We employed occlusion of middle cerebral artery (MCAO) in C57BL/6 mice. We serially measured MRI including DWI and T2WI. After MRI, we prepared brain sections or samples and examined microtubule-associated protein 2 (MAP2) expression, alpha-fodrin degradation, extravasation of albumin and claudin-5 expression. In permanent or transient MCAO for 45 min, DWI hyperintensities was already found at 60 min without change of T2, showing DWI-T2 mismatch. In permanent MCAO, MAP2 expressions were preserved, and no extravasation of albumin was observed. In transient MCAO, MAP2 immunoreaction was already lost in the lateral part of the striatum. In both models, alpha-fodrin degradation was already detected. At 180 min, T2 hyperintensities appeared, where MAP2 signal was lost and albumin extravasation was found. At 24 h, hyperintensities of DWI and T2WI was found in the whole MCA territory, where MAP2 signal was completely lost with marked albumin extravasation and alpha-fodrin degradation. Immunoreaction for claudin-5 was preserved up to 180 min. DWI-T2 mismatch area may not always indicate intactness of cytoskeletal protein but shows preservation of BBB.
磁共振成像扩散加权成像（DWI）-液体衰减反转恢复序列（FLAIR）不匹配被认为可预测4.5小时内症状发作。本研究评估了DWI-T2不匹配中细胞骨架蛋白和血脑屏障（BBB）的破坏情况。我们采用C57BL/6小鼠大脑中动脉闭塞（MCAO）模型。我们连续测量包括DWI和T2WI在内的磁共振成像。磁共振成像后，我们制备脑切片或样本，并检测微管相关蛋白2（MAP2）表达、α- fodrin降解、白蛋白外渗和claudin-5表达。在永久性或短暂性MCAO 45分钟后，60分钟时已发现DWI高信号，而T2无变化，显示DWI-T2不匹配。在永久性MCAO中，MAP2表达得以保留，未观察到白蛋白外渗。在短暂性MCAO中，纹状体外侧部分的MAP2免疫反应已经消失。在两种模型中，均已检测到α- fodrin降解。180分钟时，出现T2高信号，此时MAP2信号消失，发现白蛋白外渗。24小时时，在整个MCA区域发现DWI和T2WI高信号，此时MAP2信号完全消失，伴有明显的白蛋白外渗和α- fodrin降解。claudin-5的免疫反应在180分钟内得以保留。DWI-T2不匹配区域可能并不总是表明细胞骨架蛋白完整，但显示血脑屏障的保留。
